Books by Subject
- 2010Rebecca Rakow-Penner.Breast magnetic resonance imaging (MRI) is becoming an increasingly valuable technology for breast cancer detection, especially for women at high risk for the disease. Stanford Hospital alone performed approximately 1,000 breast MRIs last year. This demand and need to increase specificity of breast MRI motivates improving current breast MR protocols, as well as exploring new applications of MR technology to breast imaging. Most clinical breast MR exams are performed at a 1.5T field strength. 3T scanners, however, are becoming more prevalent in the clinical setting and thus the breast MR protocol needs to be tuned accordingly. The first project includes measurements of T1 and T2 of breast fat and glandular tissue at 1.5T and 3T and the corresponding recommendation for altering the TR and TE for 3T breast imaging. The beating heart posterior to the breast often produces artifacts in breast MR images. The second project is a cylindrical saturation method that reduces unwanted signal from the heart while avoiding signal loss from the breast tissue of interest. Detecting tumor oxygenation non-invasively may give insight on tumor differentiation, predict susceptibility to antiangiogenic therapeutics, and monitor chemotherapeutics. The third project introduces the application of BOLD contrast imaging, a technique usually applied in functional brain MR imaging for characterizing tumor oxygenation in the breast.
- 2009Charles S. Lessard.
- 2008 CRCnetBASERiadh W.Y. Habash.
- 2007 SpringerRobert Plonsey and Roger C. Barr.
- 1964-edited by Madeleine F. Barnothy.
- 2013 SpringerR.N. Miftahof, H.G. Nam.
- 2010 SpringerThomas Jue, editor.Protein Structure Prediction / Patrice Koehl -- Molecular Modeling of Biomembranes: A How-to Approach / Allison N. Dickey and Roland Faller -- Introduction to Electron Paramagnetic Resonance Spectroscopy / Marcin Brynda -- Theory and Applications of Biomolecular NMR Spectroscopy / James B. Ames -- FRET and Its Biological Application as a Molecular Ruler / Jie Zheng -- Introduction to Modern Techniques in Mass Spectrometry / Caroline S. Chu and Carlito B. Lebrilla -- Transmission Electron Microscopy and Computer-Aided Image Processing for 3D Structural Analysis of Macromolecules / Dominik J. Green and R. Holland Cheng -- Raman Spectroscopy of Living Cells / Tyler Weeks and Thomas Huser.
- 2013 SpringerJonathan D. Dinman, editor.When quantum mechanics was first proposed a century ago, nobody could have anticipated how deeply it would affect our lives. Today, we are connected and powered through devices whose existence is predicated on the basic principles of this strange physics. Not even the biological sciences have escaped its reach. As scientists query the deepest mysteries of the living world, the physical scales probed and the types of questions asked are increasingly blurring the lines between biology and physics. The hybrid field of biophysics represents the new frontier of the 21st century. The ribosome has been at the heart of three Nobel Prizes. Understanding its essential nature and how it interacts with other proteins and nucleic acids to control protein synthesis has been one of the central foundations in our understanding of the biology at the molecular level. With the advent of atomic scale structures, methods to visualize and separate individual molecules, and the computational power to model the complex interactions of over a million atoms at once, our understanding of how gene expression is controlled at the level of protein translation is now deeply ensconced in the biophysical realm. This book provides a premier resource to a wide audience, whether it be the general reader seeking a broad view of the field, a clinician interested in the role of protein translation in human disease, the bench researcher looking for state-of-the-art technologies, or computational scientists involved in cutting edge molecular modeling.
- v. 1, 1958.John T. Edsall, Jeffries Wyman.
- 2011 SpringerEngelbert Buxbaum
- 2015 ScienceDirectedited by Ewa K. Paluch.
- v. 1-, 2013- SpringerAllewell, Norma M.
- 2013 SpringerLinda O. Narhi, editor.This book can be used to provide insight into this important application of biophysics for those who are planning a career in protein therapeutic development, and for those outside this area who are interested in understanding it better. The initial chapters describe the underlying theory, and strengths and weaknesses of the different techniques commonly used during therapeutic development. The majority of the chapters discuss the applications of these techniques, including case studies, across the product lifecycle from early discovery, where the focus is on identifying targets, and screening for potential drug product candidates, through expression and purification, large scale production, formulation development, lot-to-lot comparability studies, and commercial support including investigations.
- 2016 SpringerMark C. Leake, editors.The biophysics of infection / Mark C. Leake -- Single-molecule observation of DNA replication repair pathways in E. coli / Adam J.M. Wollman, Aisha H. Syeda, Peter McGlynn and Mark C. Leake -- Investigating the swimming of microbial pathogens using digital holography / K.L. Thornton, R.C. Findlay, P.B. Walrad and L.G. Wilson -- What is the 'minimum inhibitory concentration' (mic) of pexiganan acting on escherichia coli?--a cautionary case study / Alys K. Jepson, Jana Schwarz-Linek, Lloyd Ryan, Maxim G. Ryadnov and Wilson C.K. Poon -- Evolution of drug resistance in bacteria / B. Waclaw -- Using biophysics to monitor the essential protonmotive force in bacteria / Mei-Ting Chen and Chien-Jung Lo -- The Type I restriction enzymes as barriers to horizontal gene transfer: determination of the DNA target sequences recognised by livestock-associated methicillin-resistant Staphylococcus aureus clonal complexes 133/ST771 and 398 / Kai Chen, Augoustinos S. Stephanou, Gareth A. Roberts, John H. White, Laurie P. Cooper, Patrick J. Houston, Jodi A. Lindsay and David T.F. Dryden -- Biomechanical analysis of infectious biofilms / David Head -- Designing a single-molecule biophysics tool for characterising DNA damage for techniques that kill infectious pathogens through DNA damage effects / Helen Miller, Adam J.M. Wollman and Mark C. Leake -- Bacterial surfaces: front lines in host-pathogen interaction / Jane E. King and Ian S. Roberts -- Biophysical approaches to bacterial gene regulation by riboswitches / Cibran Perez-Gonzalez, Jonathan P. Grondin, Daniel A. Lafontaine and J. Carlos Penedo -- Bugs on a slippery plane / Dmitri O. Pushkin and Martin A. Bees -- Transcription regulation and membrane stress management in enterobacterial pathogens / Nan Zhang, Goran Jovanovic, Christopher McDonald, Oscar Ces, Xiaodong Zhang and Martin Buck -- How biophysics may help us understand the flagellar motor of bacteria which cause infections / Matthew A.B. Baker -- Mechanics of bacterial cells and initial surface colonization / Sebastian Aguayo and Laurent Bozec -- Neutron reflectivity as a tool for physics-based studies of model bacterial membranes / Robert D. Barker, Laura E. McKinley and Simon Titmuss -- Mechanisms of Salmonella typhi host restriction / Stefania SpanoÌ€ --Insights into biological complexity from simple foundations / L. Albergante, D. Liu, S. Palmer and T.J. Newman -- Force spectroscopy in studying infection / Zhaokun Zhou and Mark C. Leake -- Imaging immunity in lymph nodes: past, present and future / James Butler, Amy Sawtell, Simon Jarrett, Jason Cosgrove, Roger Leigh, Jon Timmis and Mark Coles -- Novel approaches to manipulating bacterial pathogen biofilms: whole-systems design philosophy and steering microbial evolution / Alexandra S. Penn -- Index.Also available: Print – 2016
- 2014 SpringerJohn Golbeck, Art van der Est, editors."The volume is intended as an introduction to the physical principles governing the main processes that occur in photosynthesis, with emphasis on the light reactions and electron transport chain. A unique feature of the photosynthetic apparatus is the fact that the molecular structures are known in detail for essentially all of its major components. The availability of this data has allowed their functions to be probed at a very fundamental level to discover the design principles that have guided evolution. Other volumes on photosynthesis have tended to focus on single components or on a specific set of biophysical techniques, and the authors' goal is to provide new researchers with an introduction to the overall field of photosynthesis. The book is divided into sections, each dealing with one of the main physical processes in photosynthetic energy conversion. Each section has several chapters each describing the role that a basic physical property, such as charge or spin, plays in governing the process being discussed. The chapters proceed in an orderly fashion from a quantum mechanical description of early processes on an ultrafast timescale to a classical treatment of electron transfer and catalysis on a biochemical timescale culminating in evolutionary principles on a geological timescale."--Publisher's website.
- 2013 SpringerRick Russell, editor.Structured RNAs are everywhere, functioning throughout gene expression with key roles ranging from catalysis to regulation. New functional RNAs are being discovered all the time; in fact, it is now clear that a much greater fraction of eukaryotic genomes is devoted to coding for RNA than protein. Many of these RNAs must traverse complex energy landscapes to find their functional three-dimensional structures. Along the way, they may encounter native and non-native folding intermediates, chaperone proteins, and assemble with partner proteins. This volume, written by experts in the field, discusses the current understanding of the biophysical principles that govern RNA folding, with featured RNAs including the ribosomal RNAs, viral RNAs, and self-splicing introns. In addition to the fundamental features of RNA folding, the central experimental and computational approaches in the field are presented with an emphasis on their individual strengths and limitations, and how they can be combined to be more powerful than any method alone; these approaches include NMR, single molecule fluorescence, site-directed spin labeling, structure mapping, comparative sequence analysis, graph theory, course-grained 3D modeling, and more. This volume will be of interest to professional researchers and advanced students entering the field of RNA folding.
- 2013 WileyJianqing Wang, Qiong Wang.Introduction to Body Area Communications -- Electromagnetic Characteristics of the Human Body -- Electromagnetic Analysis Methods -- Body Area Channel Modeling -- Modulation/Demodulation -- Body Area Communication Performance -- Electromagnetic Compatibility Considerations -- Summary and Future Challenges.
- 2006 Springeredited by Bernhard Grimm ... [et al.].
- 2011Karen Lynn Havenstrite.The ultimate goal of regenerative medicine is to repair tissues damaged by aging, injury or disease. Tissue-specific adult stem cells constitute a reservoir of cells in postnatal tissue that have the remarkable capacity to proliferate and repair tissue damage because they can both self-renew, or produce more stem cells, and differentiate into mature cells. Adult stem cells have been identified in a variety of tissues, including blood, brain, skin, intestine, and muscle and methods exist to prospectively isolate these populations by flow cytometry. Upon transplantation, they possess an extraordinary ability to contribute extensively to tissue regeneration. Notably, adult stem cells are a relatively rare cell population and methods to propagate and expand these cell types in culture without loss of regenerative capacity are lacking, a hurdle to their clinical use. In vivo, stem cells reside in an instructive microenvironment, or niche, which serves to regulate fate decisions, including quiescence, self-renewal, and differentiation. Given the complexity of their native environment, it is not surprising that upon removal from their niche they rapidly lose regenerative capacity. While the role of biochemical signals in regulating stem cell fate and function has been widely explored, the effects of biophysical signals have not been discerned. To elucidate the role of matrix elasticity in regulating adult stem cell fate, we first design a biomimetic hydrogel culture platform to mimic tissue elasticity and physiologic presentation of biochemical cues. Adapting a previously described conjugate addition reaction, poly(ethylene glycol) hydrogel substrates are fabricated which have a Young's modulus that is tunable in the physiologic range (1-50kPa). Gels are designed to have limited post-polymerization swelling to enable constant density of tethered biological ligands. Utilizing this tunable hydrogel culture platform, we provide the first definitive evidence that matrix elasticity regulates adult stem cell self-renewal in culture. Using a combination of culture studies and in vivo functional assays in mice, we demonstrate that substrate rigidity profoundly impacts the self-renewal potential of tissue-specific adult stem cells isolated from skeletal muscle and bone marrow. In contrast with rigid tissue culture plastic in which regenerative potential is lost, we demonstrate that culture on a pliant hydrogel substrate maintains the 'stemness' of muscle stem cells (MuSCs) and hematopoetic stem cells (HSCs). Further, we describe a novel in vivo screen and identify an extracellular matrix molecule which, in conjunction with soft hydrogel, has a previously unrecognized role in regulating HSC fate. These studies demonstrate that recapitulating tissue rigidity, a key component of the in vivo microenvironment, enables propagation of functional adult stem cells in culture for the first time. We expect these experimental approaches will be broadly applicable to other adult stem cell types and ultimately will profoundly impact regenerative medicine by enabling generation of functional stem cell populations for use in clinical cell-based therapies.
- Derlin-1 is a rhomboid pseudoprotease required for the dislocation of misfolded proteins from the endoplasmic reticulum2011Ethan J. Greenblatt.The degradation of misfolded secretory proteins is ultimately mediated by the ubiquitin-proteasome system in the cytoplasm, therefore endoplasmic reticulum-associated degradation (ERAD) substrates must be dislocated across the ER membrane through a process driven by the AAA ATPase p97/VCP. Derlins recruit p97/VCP and have been proposed to be part of the dislocation machinery. Here we report that Derlins are inactive members of the rhomboid family of intramembrane proteases and bind p97/VCP through C-terminal SHP boxes. Human Derlin-1 harboring mutations within the rhomboid domain stabilized mutant [alpha]-1 antitrypsin (NHK) at the cytosolic face of the ER membrane without disrupting the p97/VCP interaction. We propose that substrate interaction and p97/VCP recruitment are separate functions that are essential for dislocation and can be assigned respectively to the rhomboid domain and the C terminus of Derlin-1. These data suggest that intramembrane proteolysis and protein dislocation share unexpected mechanistic features.
- 2013 Springer Protocolsedited by Ingeborg Schmidt-Krey, Yifan Cheng.Introduction to electron crystallography / Werner Kuhlbrandt -- Practical aspects in expression and purification of membrane proteins for structural analysis / Kutti R. Vinothkumar, Patricia C. Edwards, and Joerg Standfuss -- Two-dimensional crystallization of membrane proteins by reconstitution through dialysis / Matthew C. Johnson [and others] -- Monolayer two-dimensional crystallization of membrane proteins / Luc Lebeau and Catherine Venien-Bryan -- Screening for two-dimensional crystals by transmission electron microscopy of negatively stained samples / Tina M. Dreaden [and others] -- Low dose techniques and cryo-electron microscopy / Yoshinori Fujiyoshi -- Grid preparation for cryo-electron microscopy / Nobuhiko Gyobu -- Recording high-resolution images of two-dimensional crystals of membrane proteins / Agustin Avila-Sakar [and others] -- Collection of high-resolution electron diffraction data / Tamir Gonen -- Image processing of 2D crystal images / Marcel Arheit [and others] -- Merging of image data in electron crystallography / Marcel Arheit [and others] -- Evaluation of electron crystallographic data from images of two-dimensional crystals / Vinzenz M. Unger -- Modeling, docking, and fitting of atomic structures to 3D maps from cryo-electron microscopy / Gregory S. Allen and David L. Stokes -- Phasing electron diffraction data by molecular replacement : strategy for structure determination and refinement / Goragot Wisedchaisri and Tamir Gonen -- High-throughput methods for electron crystallography / David L. Stokes [and others] -- Automated grid handling and image acquisition for two-dimensional crystal screening / Anchi Cheng -- Automation of data acquisition in electron crystallography / Anchi Cheng -- Automation of image processing in electron crystallography / Marcel Arheit [and others] -- Choice and maintenance of equipment for electron crystallography / Deryck J. Mills and Janet Vonck -- Future developments in instrumentation for electron crystallography / Kenneth H. Downing -- Tubular crystals and helical arrays : structural determination of HIV-1 capsid assemblies using iterative helical real-space reconstruction / Peijun Zhang, Xin Meng, and Gongpu Zhao -- Single particle electron microscopy / Wilson C.Y. Lau and John L. Rubinstein -- Electron tomography of paracrystalline 2D arrays / Hanspeter Winkler, Shenping Wu, and Kenneth A. Taylor -- High-resolution imaging of 2D outer membrane protein F crystals by atomic force microscopy / Dimitrios Fotiadis and Daniel J. Muller -- Determination of soluble and membrane protein structures by x-ray crystallography / Raquel L. Lieberman, Mary E. Peek, and J. Derrick Watkins -- Solution nuclear magnetic resonance spectroscopy / James J. Chou and Remy Sounier -- Structure-function insights of membrane and soluble proteins revealed by electron crystallography / Tina M. Dreaden [and others] -- Lipid monolayer and sparse matrix screening for growing two-dimensional crystals for electron crystallography : methods and examples / Mark Yeager, Kelly A. Dryden, and Barbie K. Ganser-Pornillos -- Processing of electron diffraction patterns with the XDP program / Kaoru Mitsuoka -- Future directions of electron crystallography / Yoshinori Fujiyoshi.
- Fluorescence spectroscopy in biology : advanced methods and their applications to membranes, proteins, DNA, and cells2005 Springervolume editors, M. Hof, R. Hutterer, V. Fidler.Pt. 1. Fluorescence spectroscopy: basics and advanced approaches. Basics of fluorescence spectroscopy in biosciences / M. Hof, V. Fidler and R. Hutterer -- Pulse and phase fluorometries: an objective comparison / B. Valeur -- Non-exponential fluorescence of electronically coupled donors contains distance information / S. Kalinin, M. Isaksson and L.B.-Å. Johansson -- Fluorescence nanotomography: recent progress, constraints and opportunities / O.J. Rolinski and D.J.S. Birch -- Solvent relaxation as a tool for probing micro-polarity and -fluidity / J. Sýkora, R. Hutterer and M. Hof -- Total internal reflection fluorescence microscopy: applications in biophysics / N.L. Thompson and J.K. Pero -- Single molecule spectroscopy: basics and applications / J. Enderlein -- Pt. 2. Application of fluorescence spectroscopy to biological membranes. Raft microdomains in model membranes as revealed by fluorescence quenching / G. Duportail -- The lateral structure of lipid membranes as seen by fluorescence microscopy / L.A. Bagatolli -- Pt. 3. Application of fluorescence spectroscopy to protein studies. Protein dynamics and protein folding dynamics revealed by time-resolved fluorescence / A. Saxena, J.B. Upgaonkar and G. Krishnamoorthy -- Time-resolved fluorescence and two-photon FCS investigation of the interaction of HIV-1 nucleocapsid protein with hairpin loop oligonucleotides / J. Azoulay ... [et al.] -- Pt. 4. Application of fluorescence spectroscopy to DNA and drug delivery. Fluorescence techniques in non-viral gene therapy / N. Adjimatera, A.P. Neal and I.S. Blagbrough -- Fluorescence applications in targeted drug delivery / K. Bryl and M. Langner -- Pt. 5. Fluorescence spectroscopy in cells: FCS and quantum dots. Fluorescence correlations spectroscopy in cell biology / B. Brock -- Fluorescence quantum dots: properties and applications / M.R. Warnement and S.J. Rosenthal -- Heat stress of cancer cells: fluorescence imaging of structural changes with quantum dots 605 and alexa 488.
- 2012Joshua Asher Weinstein.The adaptive immune system enables individuals to defend against previously un-encountered pathogens by trial and error. It does so by employing receptors, known as antibodies, whose active genetic diversification fine-tunes this defensive response. Tremendous progress has been made in understanding the mechanisms by which antibodies develop and signal activation. However, it was not until a few years ago, with the advent of affordable in-house high-throughput DNA sequencing, and our publication of whole zebrafish antibody repertoires, that any organism's antibody diversity was characterized comprehensively. In this dissertation, we demonstrate the power of this "top-down" approach to illuminate global, system-wide changes of immune receptor repertoires during organism development and immune response. Special attention is given to applying these measurements to build predictive dynamical models that elucidate the interplay between antibody-sequences and the B-cells that produce them. While we use zebrafish liberally as a model organism for these purposes, cross-species comparisons establish far more general principles of repertoire organization. We go further to evaluate the efficacy of high-throughput immune receptor sequencing to advance clinical goals by inferring which vaccines were received by human patients based on antibody-sequences obtained from whole blood afterward. Finally, we demonstrate the usefulness of single B-cell measurements to correlate antibody mutations to gene expression, thereby providing insight into how these variables co-vary system-wide. This work serves to illustrate the potential of global characterizations of antibody repertoires for providing newer and clearer pictures of immune dynamics in general.
- Handbook of biological effects of electromagnetic fields. Bioengineering and biophysical aspects of electromagnetic fields. 3rd ed.2007 CRCnetBASEedited by Frank S. Barnes, Ben Greenebaum.Introduction -- 1. Environmental and Occupationally Encountered Electromagnetic Fields / Kjell Hansson Mild and Ben Greenebaum -- 2. Endogenous Electric Fields in Animals / Richard Nuccitelli -- 3. Dielectric Properties of Biological Materials / Camelia Gabriel -- 4. Magnetic Properties of Biological Material / Jon Dobson -- 5. Interaction of Direct Current and Extremely Low-Frequency / Electric Fields with Biological Materials and Systems / Frank S. Barnes -- 6. Magnetic Field Effects on Free Radical Reactions in Biology / Stefan Engström -- 7. Signals, Noise, and Thresholds / James C. Weaver and Martin Bier -- 8. Biological Effects of Static Magnetic Fields / Shoogo Ueno and Tsukasa Shigemitsu -- 9. The Ion Cyclotron Resonance Hypothesis / A.R. Liboff -- 10. Computational Methods for Predicting Field Intensity and Temperature Change / James C. Lin and Paolo Bernardi -- 11. Experimental EMF Exposure Assessment / Sven Kühn and Niels Kuster -- 12. Electromagnetic Imaging of Biological Systems / William T. Joines, Qing H. Liu, and Gary Ybarra.
- 2014 Wileyedited by Konstantina S. Nikita.
- 2010 CRCnetBASEedited by Robert Splinter.
- 2010Lawrence Otto Klein.This thesis is organized in four chapters. Chapter I is intended to give a general introduction to αβ T cells, their role in the immune system, their T cell receptor (TCR), and the specific TCR transgenic system used in this work. In chapter II the TCR signaling pathway is introduced, and a photoactivation method we developed for interrogating proximal events in this pathway is described. We describe experiments using this method that defined delay times between TCR-pMHC binding and initiation of various TCR proximal signaling events. We found delays much shorter than previous measurements suggested, and propose that they may represent a feature of the pathway predicted by the kinetic-proofreading model of TCR signaling. In this chapter we also describe experiments that took advantage of the ability to precisely define a sub-cellular region of TCR stimulation to interrogate the spatial dynamics of TCR signaling. We found that the T cell membrane was compartmentalized such that even rapidly diffusible second-messengers were confined to the local region of stimulation. By stimulating distinct regions of T cells sequentially, we showed that desensitization occurred rapidly in some branches of the TCR signaling pathway but not at all in others. In chapter III we introduce previous research that sought to define properties of the TCR-pMHC interaction that determine stimulatory potency, and explain how these studies have led to interest in measuring kinetic parameters of the TCR-pMHC interaction in a native two-dimensional environment. We describe development of a new method to measure two-dimensional kinetics using a combination of our photoactivation system and direct detection of receptor-ligand binding via FRET. Using this method we showed that the rate of pMHC binding in a T cell contact interface was not influenced by a variety of cellular factors, but was defined by the kinetics of TCR-pMHC binding measured in vitro. We developed a quantitative method for analyzing our data and found that it fit very well to a simple bimolecular binding model, yielding kinetic parameters in clear agreement with 3D in vitro measurements. Our technique allowed direct, bulk measurement of 2D receptor-ligand binding and has the potential to measure kinetics too fast to measure by previous methods. Finally, in chapter IV we discuss earlier work describing molecular movements that occur during formation of the T cell-APC contact, called the immunological synapse. We describe the results of a series of experiments using our combined FRET and photoactivation assay that revealed the dynamics of TCR-pMHC interactions during immunological synapse formation. Our experiments showed that ligand binding was initiated in small clusters that were stable for tens of seconds while being actively transported toward the center of the cell. We describe the interesting observations that TCR-pMHC binding occurred in a distribution more heterogeneous than either the receptor or ligand distribution, and was regulated by cytoskeletal activity. We showed that in naïve cells this distribution was markedly different than in antigen-experienced cells, indicating that these two cell types may search for antigen in different ways. The results in this chapter indicate that molecular interactions in the synapse are actively regulated by cellular processes and are much more complex than would be expected from measurements of molecular distributions.
- 2003 CRCnetBASEJack Tuszynski, Michal Kurzynski.
- [v. 7], 2016edited by Alexander Stone Macnow, MD.Kinematics and Dynamics -- Work and Energy -- Thermodynamics -- Fluids -- Electrostatics and Magnetism -- Circuits -- Waves and Sound -- Light and Optics -- Atomic and Nuclear Phenomena -- Mathematics -- Reasoning About the Design and Execution of Research -- Data-Based and Statistical Reasoning.
- Mechanistic studies and biomedical applications of antimicrobial peptoids against multi-drug resistant bacterial infections2011Rinki Kapoor.The increasing prevalence of chronic, difficult-to-treat resistant bacterial infections have created a pressing need for the discovery of promising, novel pharmaceutical candidates that could replace or complement current therapies, which are becoming less reliable and effective due to a rise in bacterial resistance. Antimicrobial peptides (AMPs) are a naturally occurring, ubiquitous, and ancient class of antibiotics that offer a unique template for the development of novel antimicrobial therapies. However, in vivo therapeutic peptides have a short half-life since they are easily degraded by proteases, thus reducing their bioavailability, which renders them a less attractive choice therapeutically. Consequently, non-natural mimics of AMPs, which can emulate the favorable characteristics of AMPs are becoming significantly important. Poly-N-substituted glycines, also called "Peptoids", are structural and functional mimics of AMPs and are resistant to proteolysis. Predecessors in the Barron laboratory designed and characterized antimicrobial peptoids against free-floating, planktonic bacteria. However, almost 60% of infections are caused by bacterial biofilms. These complex communities of microorganisms are protected by an excreted matrix of adhesive biomacromolecules and are more difficult to kill with conventional antibiotics than planktonic bacteria. Furthermore, to develop peptoids as potential therapeutics, the mechanisms by which they interact with bacteria need to be understood, which are still under investigation. Here, we report that peptoids have similar or better efficacy than conventional antibiotics against biofilms of a clinical isolate of drug-resistant P. aeruginosa. We determined the effects of peptoids on bacterial biomass and cell viability, by Crystal Violet assay and bacterial plating, respectively. We also explored the efficacy of peptoids against Mycobacterium (an organism resistant to antibiotics due to the presence of a thick waxy coating) and intracellular L. monocytogenes by bioluminescent imaging. In addition, we also investigated the mechanisms of action of peptoids and peptides by biophysical techniques (Ultra-Violet Visible spectroscopy) and bioluminescent imaging. We report that peptoids are non-lytic and cause bacterial killing by aggregating the bacterial ribosomes and decreasing ATP levels inside the cell. Lastly, we present a mouse wound model, which suggests that peptoids are effective in vivo in reducing P. aeruginosa infections.
- 2005 NCBI Bookshelfedited by Andre Kamkin and Irina Kiseleva.Mechanosensitivity of cells from various tissues -- Mechanotransduction in the Nematode Caenorhabditis elegans -- Mechanically mediated crosstalk in heart -- Swelling-and stretch-activated chloride channels in the heart: regulation and function -- Role of stretch-activated channels in the heart: action potential and Ca2+ transients -- Isolated cardiomyocytes: mechanosensitivity of action potential, membrane current and ion concentration -- Mechano-electric feedback in the heart: evidence from intracellular microelectrode recordings on multicellular preparations and single cells from healthy and diseased tissue -- The Role of mechanosensitive fibroblasts in the heart -- Mechanical modulation of intracellular ion concentrations: mechanisms and electrical consequences -- Stretch-induced slow force response in mammalian ventricular myocardium -- The Na+/H+ exchanger as the main protagonist following myocardial stretch: the Anrep effect and myocardial hypertrophy -- Mechano-electric feedback and atrial arrhythmias -- The Role of mechano-electrical feedback in the cholinergic atrial fibrillation initiation --; Mechanosensitive cation channels of leech neurons -- Mechanosensitivity of primary afferent nociceptors in the pain pathway -- Stimulus-secretion coupling in the osmoreceptive prolactin cell of the tilapia -- Stretch-inactivated channels in skeletal muscle -- Stretch-activated cation channels and the myogenic response of small arteries -- Mechanobiology of bone tissue and bone cells -- Functional roles of mechanosensitive ion channels, ss1 integrins and kinase cascades in chondrocyte mechanotransduction -- Enigmatic roles of the epithelial sodium channel (ENaC) in articular chondrocytes and osteoblasts: mechanotransduction, sodium transport or extracellular sodium sensing?
- 2006 SpringerBengt Nölting.The three-dimensional structure of proteins. -- Liquid chromatography of biomolecules. -- Mass spectrometry. -- X-ray structural analysis. -- Protein infrared spectroscopy. -- Electron microscopy. -- Scanning probe microscopy. -- Biophysical nanotechnology. -- Proteomics: high throughput protein functional analysis. -- Ion mobility spectrometry. -- Ø-value analysis. -- Evolutionary computer programming. -- Conclusions.
- 2012Aaron Michael Streets.Phase transitions are ubiquitous in nature. Fundamental study of phase transition phenomena is a cornerstone of condensed matter physics, and theoretical results in this area guide technology development in material science. Phase transitions also play an important role in biology. Biological macromolecule phase transitions occur in many biological processes, for example the gel-liquid transition in lipid bilayers and amyloid formation in protein aggregation disease. From a technological standpoint, the ability to crystallize proteins has enabled one of the most important advances in biology of the last century: protein structure determination with X-ray crystallography. However, biological macromolecule phase transitions often display stark phenomenological differences from their inorganic analogs. This owes to the sheer size and complexity of proteins and nucleic acid complexes. Macromolecular phase transition theory is rich in subtleties, anecdotal & counter-intuitive results, and often diverges from predictions of classical theory. In addition to developing theory, fundamental study in this area is also critical for improvements in high-throughput crystallography efforts and in understanding mechanisms of devastating neurodegenerative diseases. This thesis approaches the study of macromolecule phase transitions through the development of new measurement technology. In this work, spectroscopic and imaging techniques are combined with microfluidic systems to provide insight into three areas of macromolecule phase transitions. First, dynamic light scattering and microscopy are integrated onto a microfluidic platform to study and optimize protein crystallization. Additionally dynamic light scattering is combined with fluorescence spectroscopy to investigate amyloid fibril aggregation. Finally, a new technology is presented that demonstrates high-throughput mapping of macromolecule structure by integrating single-molecule fluorescence resonance energy transfer spectroscopy with a microfluidic mixing platform. This lab-on-a-chip platform enables examination of conformational transitions in nucleic acids in response to changes in the chemical and molecular environment in order to create a conformational "phase diagram". In addition to presenting new insight into the mechanism of protein crystallization and protein aggregation, this thesis introduces new technologies for studying biological macromolecule phase transitions.
- 2013 SpringerNorma Allewell, Linda O. Narhi, Ivan Rayment (eds.).This volume of the series Biophysics for the Life Sciences focuses on the conceptual framework and major research tools of contemporary molecular biophysics. It is designed to enable non-specialists -both students and professionals in other fields - to understand how these approaches can be used across the biosciences and in medicine, agriculture, biotechnology, pharmaceutical development and other fields. The scope of this volume is appropriate for advanced undergraduate and graduate courses in biophysics and biophysical chemistry. The book begins with an overview of the development of molecular biophysics and a brief survey of structural, physical, and chemical principles. Subsequent chapters written by experts present, with examples, the major experimental methods: optical spectroscopy, X-ray and neutron diffraction and scattering, nuclear magnetic resonance, electron paramagnetic resonance, mass spectrometry, and single molecule methods. The relationship between the biophysical properties of biological macromolecules and their roles as molecular machines is emphasized throughout and illustrated with three examples DNA helicases, rotary motor ATPases, and myosin.The concluding chapter discusses future prospects in X-ray and neutron scattering, mass spectrometry, and pharmaceutical development.
- 2010 SpringerDilson E. Rassier, editor.
- 2010Michael Paul Bokoch.G protein coupled receptors (GPCRs) are seven transmembrane proteins that are expressed in all eukaryotic cells and tissues. These receptors play key roles in human physiology and disease. The goal of my work is to understand the molecular detail of ligand recognition by GPCRs, and how this process leads to conformational changes that manifest as cellular signaling. Meeting this goal will advance our knowledge of membrane protein biology. It will also reveal structural targets and physicochemical logic to aid pharmaceutical design. The age of GPCR structural biology recently arrived with the first x-ray structures of rhodopsin and the beta2 adrenergic receptor (beta2AR). However, membrane proteins are constantly fluctuating entities. Dynamic behavior is intrinsic to their function. As such, static x-ray structures alone are inadequate. Herein, I develop biophysical techniques to study these dynamic receptors. Using NMR spectroscopy, I characterize conformational changes in the extracellular region of the beta2AR, a surface rich with potential for drug design. I also explore the signaling properties of monomeric GPCRs and conformational changes of other macromolecules using single-molecule fluorescence. While many questions about GPCRs remain, I hope this work is a small step towards understanding these important, fascinating, and beautiful molecules.
- 2010Robert Barretto.Optical microendoscopy is an emerging modality for imaging in live subjects. Using gradient refractive index (GRIN) microlenses, microendoscopy enables subcellular-resolution imaging in deep tissues that are inaccessible by traditional imaging techniques. We present a platform of methods and technologies that build upon GRIN microendoscopy: 1) miniaturized microscopes for imaging in awake, behaving animals, 2) methods for imaging contractile dynamics in the muscles of animal and human subjects, 3) chronic brain preparations that allow for longitudinal examinations of subcellular neuronal features and disease progression, and 4) novel microendoscope probes whose imaging capabilities approach that of standard water-immersion microscope objectives. When combined with the broad sets of available fluorescent reporters, and minimally invasive surgical preparations, the work described in this dissertation enables sophisticated experimental designs for probing how cellular characteristics may underlie or explain behavior, in models of both healthy and diseased states.
- 2013 Springerby Gopal B. Saha.Structure of Matter -- Radioactive Decay -- Kinetics of Radioactive Decay -- Statistics of Radiation Counting -- Production of Radionuclides -- Interaction of Radiation with Matter -- Gas-Filled Detectors -- Scintillation and Semiconductor Detectors -- Gamma Cameras -- Performance Parameters of Gamma Cameras -- Digital Computers in Nuclear Medicine -- Single Photon Emission Computed Tomography -- Positron Emission Tomography -- Internal Radiation Dosimetry -- Radiation Biology -- Radiation Regulations and Protection.
- 2007 CRCnetBASED. Baltas, L. Sakelliou, N. Zamboglou.
- 2007 SpringerIrving P. Herman.Terminology, the standard human, and scaling -- Statics of the body -- Motion -- Mechanical properties of the body -- Muscles -- Metabolism: energy, heat, work, and power -- Fluid pressure, fluid flow in the body, and motion in fluids -- Cardiovascular system -- Lungs and breathing -- Sound, speech, and hearing -- Light, eyes, and vision -- Electrical and magnetic properties -- Feedback and control -- Appendix A. Symbols and units -- Appendix B. Locator of major anatomical and anthropometric information -- Appendix C. Differential equations -- Appendix D. Similar model systems -- Appendix E. Biophysics of the human body.
- 2012Andrew W. Wood ; with contributions by Anthony Bartel ... [et al.]."Preface The aim of this book is to show that many aspects of human physiology lend themselves to numerical analysis. Many ways of monitoring physiological function also rely on an understanding of physics and engineering to appreciate fully how they operate. The book arises out of an undergraduate course in medical biophysics and a postgraduate course in biomedical instrumentation the authors were involved in for many years. Although the emphasis is on numerical analysis only, a basic knowledge of mathematics is assumed and every effort is made to supplement mathematical formulae with qualitative explanations and illustrations to encourage an intuitive grasp on the processes involved. Most of the chapters have a range of numerical tutorial problems with, in most cases, worked solutions. These are based on examination questions at the middle and senior undergraduate level. For some of the material, the computational package MATLABʼ offers a convenient way to gain insight into some of the more advanced mathematical analysis of physiological or of clinical monitoring systems. Suitable MATLAB code is provided where this might aid understanding. I acknowledge the help of colleagues in the preparation of this book. Particular chapters have been authored as follows: Anthony Bartel, Per Line, Peter Cadusch, Joseph Ciorciari, David and Sheila Crewther, John Patterson , Mark Schier, Bruce Thompson. In addition, others have been associated with teaching the course over many years. These include: Peter Alabaster, David Liley, Ric Roberts and David Simpson"--Provided by publisher.
- 2011Brad Busse.Array tomography (AT) is a high-resolution proteomic imaging method that exploits a combination of light and EM techniques to resolve fine details at the synapse level across large fields of view spanning entire circuits. Much of my graduate work has centered on helping to shape AT into an imaging method fit for rigorous use, by developing computational algorithms which take advantage of AT's particular qualities to automate its operation. Among them are: a mapping tool for microscopy software to automate the imaging of AT's unique section layout; Multistackreg, an alignment plugin which is capable of registering multiple imaging sessions on the same piece of tissue; a cross-correlation algorithm for fluorescent channel validation; the synaptogram, a tool for visualizing synapse-scale high-dimensional proteomic molecular complexes; and an active learning paradigm for large-scale synapse quantification.
- 2010 ScienceDirectedited by Nils G. Walter.Star polymer surface passivation for single-molecule detection / Jürgen Groll and Martin Moeller -- Azide-specific labeling of biomolecules by Staudinger-Bertozzi ligation: phosphine derivatives of fluorescent probes suitable for single-molecule fluorescence spectroscopy / Anirban Chakraborty ... [et al.] -- Preparation of fluorescent pre-mRNA substrates for an smFRET study of pre-mRNA splicing in yeast / John Abelson, Haralambos Hadjivassiliou and Christine Guthrie -- Nanovesicle trapping for studying weak protein interactions by single-molecule FRET / Jaime J. Benítez, Aaron M. Keller and Peng Chen -- Droplet confinement and fluorescence measurement of single molecules / Lori S. Goldner, Ana M. Jofre and Jianyong Tang -- Single-molecule fluorescence spectroscopy using phospholipid bilayer nanodiscs / Abhinav Nath ... [et al.] -- Single-molecule spectroscopy using microfluidic platforms / Samuel Kim and Richard N. Zare -- Detection of protein-protein interactions in the live cell plasma membrane by quantifying prey redistribution upon bait micropatterning / Julian Weghuber ... [et al.] -- Analysis of complex single-molecule FRET time trajectories / Mario Blanco and Nils G. Walter -- Single-molecule fluorescence studies of intrinsically disordered proteins / Allan Chris M. Ferreon ... [et al.] -- Measuring the energetic coupling of tertiary contacts in RNA folding using single molecule fluorescence resonance energy transfer / Max Greenfield and Daniel Herschlag -- A highly purified, fluorescently labeled in vitro translation system for single-molecule studies of protein synthesis / Jingyi Fei ... [et al.] -- Watching individual proteins acting on single molecules of DNA / Ichiro Amitani ... [et al.] -- DNA curtains for high-throughput single-molecule optical imaging / Eric C. Greene ... [et al.] -- Scanning FCS for the characterization of protein dynamics in live cells / Zdenĕk Petrás̆ek, Jonas Ries and Petra Schwille -- Observing protein interactions and their stoichiometry in living cells by brightness analysis of fluorescence fluctuation experiments / Yan Chen ... [et al.] -- Detection of individual endogenous RNA transcripts in situ using multiple singly labeled probes / Arjin Raj and Sanjay Tyagi -- Single mRNA tracking in live cells / Hye Yoon Park, Adina R. Buxbaum and Robert H. Singer -- Single-molecule sequencing: sequence methods to enable accurate quantitation / Christopher Hart ... [et al.] -- Real-time DNA sequencing from single polymerase molecules / Jonas Korlach ... [et al.].
- Single molecule tools. Part B, Super-resolution, particle tracking, multiparameter, and force based methods. 1st ed.2010 ScienceDirectedited by Nils G. Walter.
- 2011Matthew Herbert Larson.Transcription by RNAP is highly regulated in both prokaryotic and eukaryotic cells, and the ability of the cell to differentiate and respond to its environment is largely due to this regulation. During elongation, for example, RNAP is known to momentarily halt in response to certain cellular signals, and this pause state has been implicated in the regulation of gene expression in both prokaryotic and eukaryotic organisms. In addition, once RNAP reaches the end of a gene, it must reliably terminate and release the newly-transcribed RNA, providing another potential point of regulation within different cell types. Both of these steps are crucial to ensure proper gene expression. In this dissertation, I focus on transcription elongation by both prokaryotic and eukaryotic RNA polymerases, as well as their regulation through pausing and termination. To probe the role of RNA hairpins in transcriptional pausing, a novel single-molecule "RNA-pulling" assay was used to block the formation of secondary structure in the nascent transcript. Force along the RNA did not significantly affect transcription elongation rates, pause frequencies, or pause lifetimes, indicating that short "ubiquitous" pauses are not a consequence of RNA hairpins. Force-based single-molecule techniques were also used to study the mechanism and energetics of transcription termination in bacteria. The data suggest two separate mechanisms for termination: one that involves hypertranslocation of RNAP along the DNA, and one that involves shearing of the RNA:DNA hybrid within the enzyme. In addition, a quantitative energetic model is presented that successfully predicts the termination efficiency of both wild-type and mutant terminators. Finally, the implementation of a novel optical-trapping assay capable of directly observing transcription by eukaryotic RNA polymerase II (RNAPII) molecules is described. This approach was used to probe the RNAPII nucleotide-addition cycle, as well as the role of the trigger loop (a conserved subdomain) in elongation. The results are consistent with a Brownian ratchet model of elongation which incorporates a secondary NTP binding site, and the trigger loop was found to modulate translocation, NTP binding, and catalysis, as well as substrate selection and mismatch recognition by RNAPII.
- 2010Peter Caton Anthony.Nucleic acids--DNA and RNA--are critical to life, involved in the storage and decoding of genetic information in the cell as well as the regulation and catalysis of specific biological processes. The function of a nucleic acid molecule is determined in large part by the structure it adopts, which in turn depends on its sequence. The mechanisms of sequence-directed nucleic acid folding remain incompletely understood, particularly for large RNA molecules. The work presented in this thesis uses single-molecule optical-trapping techniques to study nucleic acid folding, where reversible folding is induced and measured in individual molecules through the application of force. In Chapter 2 we demonstrate direct measurement of the full folding energy landscapes of DNA hairpins, which comprise a model system for studying nucleic acid secondary structure, and show how such landscapes are sensitive to sequence. In Chapter 3 we study the electrostatics of DNA hairpin folding by measuring trends in folding energies under different ionic conditions and comparing these trends with those predicted by Poisson-Boltzmann theory. Finally, in Chapter 4 we examine folding of the TPP riboswitch aptamer, an RNA molecule with complex secondary structure that also adopts tertiary structure upon binding a small-molecule ligand. We measured the folding energy landscape of the aptamer and perturbations of this landscape resulting from mutations and ligand binding, and propose a kinetic model to describe the coupling between aptamer folding and ligand binding. Taken together, the results presented here demonstrate the usefulness of the energy landscape framework for characterizing nucleic acid folding in conjunction with single-molecule measurements.
- 2012Kirsten Linnea Frieda.RNA--a ubiquitous and versatile type of biopolymer that is critically involved in many of life's molecular processes--is produced sequentially in single-stranded form during transcription by RNA polymerase and has the propensity to fold back on itself into interesting structures of functional import. In nature, riboswitches are elegant examples of structured RNA that adopt alternate conformations in response to ligand binding and thereby affect gene expression. We have been able to probe riboswitch conformations in novel detail using single-molecule optical-trapping techniques. These experimental approaches supply a unique perspective on folding since the ability to apply force provides an effective handle on the real-time state of individual RNA molecules and a means of modulating that state. In this dissertation, I focus on three studies that explore adenine riboswitch conformations and mechanisms. Specifically, in the first, we dissect the folding landscape of the aptamer (ligand-binding domain) of an adenine riboswitch. Extending this endeavor to full riboswitch sequences, we probe the interplay of a riboswitch aptamer with its downstream expression platform (which executes the switch's regulatory role), and develop methods to do so both during and after transcription. The second study takes full advantage of the latter ability: In a complete adenine riboswitch controlling transcription, we directly observe cotranscriptional folding of the nascent RNA in which the adopted conformation dictates whether or not to terminate transcription. Finally, in a different adenine riboswitch controlling translation, we investigate switch conformational changes and identify a series of competing structural elements that kinetically trap the riboswitch conformation, implying that the initial, cotranscriptional fold of the riboswitch may determine its gene regulatory state. These efforts enhance our understanding of folding architectures in riboswitches, specifically, and in RNA, more broadly. They further highlight the importance of cotranscriptional folding, providing a novel window into the nascent development of RNA conformations.
- 2014 SpringerMiguel A. Aon, Valdur Saks, Uwe Schlattner, editors.From Physiology, Genomes, Systems and Self-Organization to Systems Biology : The Historical Roots of a Twenty-First Century Approach to Complexity / M.A. Aon, D. Lloyd, and V. Saks -- Complex Systems Biology of Networks : The Riddle and the Challenge / Miguel A. Aon -- Systems Biology of Signaling Networks -- The Control Analysis of Signal Transduction / Hans V. Westerhoff, Samrina Rehman, Fred C. Boogerd, Nilgun Yilmaz, and Malkhey Verma -- MicroRNAs and Robustness in Biological Regulatory Networks. A Generic Approach with Applications at Different Levels : Physiologic, Metabolic and Genetic / Jacques Demongeot, Olivier Cohen, and Alexandra Henrion-Caude -- Dynamics of Mitochondrial Redox and Energy Networks : Insights from an Experimental-Computational Synergy / Sonia Cortassa and Miguel A. Aon -- Adenylate Kinase Isoform Network : A Major Hub in Cell Energetics and Metabolic Signaling / Song Zhang, Emirhan Nemutlu, Andre Terzic, and Petras Dzeja -- Systems Biology of Cellular Structures and Fluxes -- Moonlighting Function of the Tubulin Cytoskeleton : Macromolecular Architectures in the Cytoplasm / Judit Ovádi and Vic Norris -- Metabolic Dissipative Structures / Ildefonso Mtz. de la Fuente -- Systems Biology Approaches to Cancer Energy Metabolism / Alvaro Marín-Hernández, Sayra Y. López-Ramírez, Juan Carlos Gallardo-Pérez, Sara Rodríguez-Enríquez, Rafael Morena-Sánchez, and Emma Saavedra -- Systems Biology of Organ Function -- Network Dynamics in Cardiac Electrophysiology / Zhilin Qu -- Systems Level Regulation of Cardiac Energy Fluxes via Metabolic Cycles : Role of Creatine, Phosphotransfer Pathways, and AMPK Signaling / Valdur Saks, Uwe Schlattner, Malgorzata Tokarska-Schlattner, Theo Wallimann, Rafaela Bagur, Sarah Zorman, Martin Pelosse, Pierre Dos Santos, Franc̦ois Boucher, Tuuli Kaambre, and Rita Guzun -- Systems Biology of Microorganisms -- Temporal Partitioning of the Yeast Cellular Network / Douglas B. Murray, Cornelia Amariei, Kalesh Sasidharan, Rainer Machné, Miguel A. Aon, and David Lloyd -- Systems Biology and Metabolic Engineering in Bacteria / Johannes Geiselmann.
- 2007 ScienceDirectedited by Jon Lorsch.Transient kinetics, flourescence, and FRET in studies of initiation and translation in bacteria / Pohl Milon ... [et al.] -- Binding of mRNA to the bacterial translation initiation complex / Sean M. Studer and Simpson Joseph -- Real-time dynamics of ribosome-ligand interaction by time-resolved chemical probing methods / Attilio Fabbretti ... [et al] -- Overexpression and purification of mammalian mitochondrial translational initiation factor 2 and initiation factor 3 / Domenick G. Grasso ... [et al.] -- In vitro studies of archaeal translational initiation / Dario Benelli and Paola Londei -- Reconstitution of yeast translation initiation / Michael G. Acker ... [et al.] -- Assembly and analysis of eukaryotic translation initiation complexes / Andrey V. Pisarev -- Reconstitution of mammalian 48S ribosomal translation initiation complex / Romit Majumdar, Jayanta Chaudhuri, and Umadas Maitra -- Biophysical approach to studies of Cap-elF4E interaction by synthetic cap analogs / Anna Niedzwiecka ... [et al.] -- Biophysical studies of the translation initiation pathway with immobilized mRNA analogs / John E. G. McCarthy, Steven Marsden, and Tobias von der Haar -- Protection-based assays to measure aminoacyl-tRNA binding to translation initiation factors / Yves Mechulam ... [et al.] -- NMR methods for studying protein-protein interactions involved in translation initiation / Assen Marintchev, Dominique Frueh, and Gerhard Wagner -- Structural methods for studying IRES function / Jeffrey S. Kieft ... [et al.].Also available: Print – 2007
- 2011Benjamin David Almquist.Electrophysiological tools and biologic delivery systems generally rely on non-optimal methods for gaining access through cellular membranes. Electrophysiological techniques that provide intracellular access, such as patch clamping, result in membrane holes and cell death in a matter of hours, while the delivery of bioactive materials are hampered by low bioavailability following passage through the endosomal pathways. In each case, the lipid bilayer backbone of the cellular membrane presents a formidable barrier to intracellular access. As biological gatekeepers, cell membranes not only physically define everything from whole organisms to individual organelles, they also prevent unobstructed flow of molecules between the inner and outer regions of the membrane. This occurs since the hydrophobic lipid acyl tails form a narrow hydrophobic layer a few nanometers thick, which is highly unfavorable for the passage of most hydrophilic molecules. It is this region that is one of the greatest obstacles to the dream of biotechnology seamlessly and non-destructively integrating synthetic components with biological systems. This thesis contributes to the understanding of how to rationally design devices that interact specifically with this hydrophobic region. In turn, this work begins to establish design guidelines for creating non-destructive, membrane-penetrating bio-inorganic interfaces. The beginning chapters focus on the development of the "stealth" probe platform. In nature, there exist specialized transmembrane proteins capable of incorporating into lipid bilayers by replicating the lipid hydrophilic-hydrophobic-hydrophilic structure. The stealth probe design mimics this structure by creating 2-10nm hydrophobic bands on otherwise hydrophilic structures. However, since current lithographic methods do not possess the necessary resolution, a new fabrication technique using a combination of top-down fabrication with bottom-up self-assembly methods was developed. This approach uses an evaporated chrome-gold-chrome stack and focused ion beam (FIB) milling, where the exposed edge of the embedded gold layer can be specifically functionalized with a hydrophobic thiol-mediated self-assembled monolayer. Chapter 3 explores the propensity for insertion and specific interaction of the stealth probe hydrophobic band with the hydrophobic lipid bilayer core. In order to gain quantitative insight into the interaction behavior, atomic force microscopy was used in conjunction with a new, stacked lipid bilayer testing platform. By using stacks of 100's to 1000's of lipid bilayers, substrate-probe interaction artifacts can be removed while simultaneously allowing precise determination of probe location within a lipid bilayer. It was found that completely hydrophilic probes reside in the hydrophilic hydration region between bilayers, whereas hydrophobically functionalized stealth probes preferred to reside in the bilayer core. This behavior was found to be independent of hydrophobic functionalization, with butanethiol and dodecanethiol both displaying preferential localization. The subsequent chapters explore how the molecular structure of the hydrophobic band and the band thickness affect membrane-probe interface stability. The lipid stack platform provides an easy method of force-clamp testing, which enabled quantitative extrapolation of the unstressed interface strength. A series of tests with various length alkanethiols found that the crystallinity of the molecules in the hydrophobic band is the dominant factor influencing interfacial stability. Surprisingly, hydrophobicity was found to be a secondary factor, although necessary to drive spontaneous membrane integration. Molecular length was also found to play a role in determining the ultimate interfacial strength, with short chain molecules similar in length to amino acid side chains promoting the most stable interfaces. The thickness of the hydrophobic band was found to regulate the interface structure. Bands with thicknesses comparable to that of the host lipid bilayer core likely promote a fused interface geometry, similar in structure to that of transmembrane protein-lipid bilayer interfaces. Thicker bands began to transition to a 'T-junction' interface that is characterized by a lower interface stability. Interestingly, the behavior of 10nm bands were indistinguishable from completely hydrophobic probes, reinforcing the importance of nanoscale patterning for stable membrane integration. Chapter 6 builds on the results of the previous chapters by exploring how various stealth probe geometries influence adhesion behavior. In agreement with force clamp testing, short disordered monolayers displayed strong integration into the bilayer core, while crystalline monolayers displayed extremely weak integration. Preliminary adhesion testing results with human red blood cells demonstrate that the stealth probe geometry holds promise for in vitro and in vivo platforms, expanding the results of this work from simply a biophysical test system to a real world example. Finally, the behavior of two hydrophobic bands either commensurately spaced with the hydrophobic core spacing in the bilayer stack, or incommensurately spaced in order to force one band to reside in the hydrophilic hydration layer, is explored. It was found that the commensurately spaced bands display superior strength to single band tips, which is attributed to the necessity to simultaneously rupture both membrane-hydrophobic band interfaces. Conversely, the incommensurately spaced probes display a significant destabilization of the interface. This is thought to be due to the forced residence of one hydrophobic band in a hydrophilic hydration layer. This result is intriguing for biologic delivery systems, as the nuclear double membrane presents a unique barrier geometry, and a double band system may provide a facile means for penetration.
- 2008 SpringerMarkus Braun, Peter Gilch, Wolfgang Zinth (eds.).Ultrahigh-resolution optical coherence tomography using femtosecond lasers / J. G. Fujimoto ... [et al.] -- Two-photon laser scanning microscopy / A. Nimmerjahn, P. Theer, F. Helmchen -- Femtosecond lasers in ophthalmology: surgery and imaging / J. F. Bille -- Ultrafast peptide and protein dynamics by vibrational spectroscopy / P. Hamm -- Photosynthetic light-harvesting / T. Pullerits, T. Polivka, V. Sundström -- Primary photosynthetic energy conversion in bacterial reaction centers / W. Zinth, J. Wachtveitl -- Ultrafast primary reactions in the photosystems of oxygen-evolving organisms / A. R. Holzwarth -- Primary photochemistry in the photoactive yellow protein: the prototype xanthopsin / D. S. Larsen, R. van Grondelle, K. J. Hellingwerf -- Structure based kinetics by time-resolved X-ray crystallography / M. Schmidt -- Primary reactions in retinal proteins / R. Diller -- Ultrashort laser pulses in single molecule spectroscopy / E. Houstein, P. Schwille.
- 2006 CRCnetBASEedited by Mark Braiman, Vasilis G. Gregoriou.
- 2014 SpringerPeter C. Ruben, editor.A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.
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