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- Volume 47, 2018
Annual Review of Biophysics - Volume 47, 2018
Volume 47, 2018
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Structural Basis for G Protein–Coupled Receptor Signaling
Vol. 47 (2018), pp. 1–18More LessG protein–coupled receptors (GPCRs), which mediate processes as diverse as olfaction and maintenance of metabolic homeostasis, have become the single most effective class of therapeutic drug targets. As a result, understanding the molecular basis for their activity is of paramount importance. Recent technological advances have made GPCR structural biology increasingly tractable, offering views of these receptors in unprecedented atomic detail. Structural and biophysical data have shown that GPCRs function as complex allosteric machines, communicating ligand-binding events through conformational change. Changes in receptor conformation lead to activation of effector proteins, such as G proteins and arrestins, which are themselves conformational switches. Here, we review how structural biology has illuminated the agonist-induced cascade of conformational changes that culminate in a cellular response to GPCR activation.
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Collapse Transitions of Proteins and the Interplay Among Backbone, Sidechain, and Solvent Interactions
Vol. 47 (2018), pp. 19–39More LessProteins can collapse into compact globules or form expanded, solvent-accessible, coil-like conformations. Additionally, they can fold into well-defined three-dimensional structures or remain partially or entirely disordered. Recent discoveries have shown that the tendency for proteins to collapse or remain expanded is not intrinsically coupled to their ability to fold. These observations suggest that proteins do not have to form compact globules in aqueous solutions. They can be intrinsically disordered, collapsed, or expanded, and even form well-folded, elongated structures. This ability to decouple collapse from folding is determined by the sequence details of proteins. In this review, we highlight insights gleaned from studies over the past decade. Using a polymer physics framework, we explain how the interplay among sidechains, backbone units, and solvent determines the driving forces for collapsed versus expanded states in aqueous solvents.
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Measuring Entropy in Molecular Recognition by Proteins
Vol. 47 (2018), pp. 41–61More LessMolecular recognition by proteins is fundamental to the molecular basis of biology. Dissection of the thermodynamic landscape governing protein–ligand interactions has proven difficult because determination of various entropic contributions is quite challenging. Nuclear magnetic resonance relaxation measurements, theory, and simulations suggest that conformational entropy can be accessed through a dynamical proxy. Here, we review the relationship between measures of fast side-chain motion and the underlying conformational entropy. The dynamical proxy reveals that the contribution of conformational entropy can range from highly favorable to highly unfavorable and demonstrates the potential of this key thermodynamic variable to modulate protein–ligand interactions. The dynamical so-called entropy meter also refines the role of solvent entropy and directly determines the loss in rotational–translational entropy that occurs upon formation of high-affinity complexes. The ability to quantify the roles of entropy through an entropy meter based on measurable dynamical properties promises to highlight its role in protein function.
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Assembly of COPI and COPII Vesicular Coat Proteins on Membranes
Vol. 47 (2018), pp. 63–83More LessIn eukaryotes, distinct transport vesicles functionally connect various intracellular compartments. These carriers mediate transport of membranes for the biogenesis and maintenance of organelles, secretion of cargo proteins and peptides, and uptake of cargo into the cell. Transport vesicles have distinct protein coats that assemble on a donor membrane where they can select cargo and curve the membrane to form a bud. A multitude of structural elements of coat proteins have been solved by X-ray crystallography. More recently, the architectures of the COPI and COPII coats were elucidated in context with their membrane by cryo-electron tomography. Here, we describe insights gained from the structures of these two coat lattices and discuss the resulting functional implications.
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Imaging mRNA In Vivo, from Birth to Death
Vol. 47 (2018), pp. 85–106More LessRNA is the fundamental information transfer system in the cell. The ability to follow single messenger RNAs (mRNAs) from transcription to degradation with fluorescent probes gives quantitative information about how the information is transferred from DNA to proteins. This review focuses on the latest technological developments in the field of single-mRNA detection and their usage to study gene expression in both fixed and live cells. By describing the application of these imaging tools, we follow the journey of mRNA from transcription to decay in single cells, with single-molecule resolution. We review current theoretical models for describing transcription and translation that were generated by single-molecule and single-cell studies. These methods provide a basis to study how single-molecule interactions generate phenotypes, fundamentally changing our understating of gene expression regulation.
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Nanodiscs: A Controlled Bilayer Surface for the Study of Membrane Proteins
Vol. 47 (2018), pp. 107–124More LessThe study of membrane proteins and receptors presents many challenges to researchers wishing to perform biophysical measurements to determine the structure, function, and mechanism of action of such components. In most cases, to be fully functional, proteins and receptors require the presence of a native phospholipid bilayer. In addition, many complex multiprotein assemblies involved in cellular communication require an integral membrane protein as well as a membrane surface for assembly and information transfer to soluble partners in a signaling cascade. Incorporation of membrane proteins into Nanodiscs renders the target soluble and provides a native bilayer environment with precisely controlled composition of lipids, cholesterol, and other components. Likewise, Nanodiscs provide a surface of defined area useful in revealing lipid specificity and affinities for the assembly of signaling complexes. In this review, we highlight several biophysical techniques made possible through the use of Nanodiscs.
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The Jigsaw Puzzle of mRNA Translation Initiation in Eukaryotes: A Decade of Structures Unraveling the Mechanics of the Process
Vol. 47 (2018), pp. 125–151More LessTranslation initiation in eukaryotes is a highly regulated and rate-limiting process. It results in the assembly and disassembly of numerous transient and intermediate complexes involving over a dozen eukaryotic initiation factors (eIFs). This process culminates in the accommodation of a start codon marking the beginning of an open reading frame at the appropriate ribosomal site. Although this process has been extensively studied by hundreds of groups for nearly half a century, it has been only recently, especially during the last decade, that we have gained deeper insight into the mechanics of the eukaryotic translation initiation process. This advance in knowledge is due in part to the contributions of structural biology, which have shed light on the molecular mechanics underlying the different functions of various eukaryotic initiation factors. In this review, we focus exclusively on the contribution of structural biology to the understanding of the eukaryotic initiation process, a long-standing jigsaw puzzle that is just starting to yield the bigger picture.
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Hemagglutinin-Mediated Membrane Fusion: A Biophysical Perspective
Vol. 47 (2018), pp. 153–173More LessInfluenza hemagglutinin (HA) is a viral membrane protein responsible for the initial steps of the entry of influenza virus into the host cell. It mediates binding of the virus particle to the host-cell membrane and catalyzes fusion of the viral membrane with that of the host. HA is therefore a major target in the development of antiviral strategies. The fusion of two membranes involves high activation barriers and proceeds through several intermediate states. Here, we provide a biophysical description of the membrane fusion process, relating its kinetic and thermodynamic properties to the large conformational changes taking place in HA and placing these in the context of multiple HA proteins working together to mediate fusion. Furthermore, we highlight the role of novel single-particle experiments and computational approaches in understanding the fusion process and their complementarity with other biophysical approaches.
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Cryo-EM Studies of Pre-mRNA Splicing: From Sample Preparation to Model Visualization
Vol. 47 (2018), pp. 175–199More LessThe removal of noncoding introns from pre-messenger RNA (pre-mRNA) is an essential step in eukaryotic gene expression and is catalyzed by a dynamic multi-megadalton ribonucleoprotein complex called the spliceosome. The spliceosome assembles on pre-mRNA substrates by the stepwise addition of small nuclear ribonucleoprotein particles and numerous protein factors. Extensive remodeling is required to form the RNA-based active site and to mediate the pre-mRNA branching and ligation reactions. In the past two years, cryo-electron microscopy (cryo-EM) structures of spliceosomes captured in different assembly and catalytic states have greatly advanced our understanding of its mechanism. This was made possible by long-standing efforts in the purification of spliceosome intermediates as well as recent developments in cryo-EM imaging and computational methodology. The resulting high-resolution densities allow for de novo model building in core regions of the complexes. In peripheral and less ordered regions, the combination of cross-linking, bioinformatics, biochemical, and genetic data is essential for accurate modeling. Here, we summarize these achievements and highlight the critical steps in obtaining near-atomic resolution structures of the spliceosome.
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Structure and Dynamics of Membrane Proteins from Solid-State NMR
Vol. 47 (2018), pp. 201–222More LessSolid-state nuclear magnetic resonance (SSNMR) spectroscopy elucidates membrane protein structures and dynamics in atomic detail to yield mechanistic insights. By interrogating membrane proteins in phospholipid bilayers that closely resemble biological membranes, SSNMR spectroscopists have revealed ion conduction mechanisms, substrate transport dynamics, and oligomeric interfaces of seven-transmembrane helix proteins. Research has also identified conformational plasticity underlying virus-cell membrane fusions by complex protein machineries, and β-sheet folding and assembly by amyloidogenic proteins bound to lipid membranes. These studies collectively show that membrane proteins exhibit extensive structural plasticity to carry out their functions. Because of the inherent dependence of NMR frequencies on molecular orientations and the sensitivity of NMR frequencies to dynamical processes on timescales from nanoseconds to seconds, SSNMR spectroscopy is ideally suited to elucidate such structural plasticity, local and global conformational dynamics, protein-lipid and protein-ligand interactions, and protonation states of polar residues. New sensitivity-enhancement techniques, resolution enhancement by ultrahigh magnetic fields, and the advent of 3D and 4D correlation NMR techniques are increasingly aiding these mechanistically important structural studies.
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The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition
Vol. 47 (2018), pp. 223–250More LessBiomolecular recognition can be stubborn; changes in the structures of associating molecules, or the environments in which they associate, often yield compensating changes in enthalpies and entropies of binding and no net change in affinities. This phenomenon—termed enthalpy/entropy (H/S) compensation—hinders efforts in biomolecular design, and its incidence—often a surprise to experimentalists—makes interactions between biomolecules difficult to predict. Although characterizing H/S compensation requires experimental care, it is unquestionably a real phenomenon that has, from an engineering perspective, useful physical origins. Studying H/S compensation can help illuminate the still-murky roles of water and dynamics in biomolecular recognition and self-assembly. This review summarizes known sources of H/S compensation (real and perceived) and lays out a conceptual framework for understanding and dissecting—and, perhaps, avoiding or exploiting—this phenomenon in biophysical systems.
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Modeling Cell Size Regulation: From Single-Cell-Level Statistics to Molecular Mechanisms and Population-Level Effects
Po-Yi Ho, Jie Lin, and Ariel AmirVol. 47 (2018), pp. 251–271More LessMost microorganisms regulate their cell size. In this article, we review some of the mathematical formulations of the problem of cell size regulation. We focus on coarse-grained stochastic models and the statistics that they generate. We review the biologically relevant insights obtained from these models. We then describe cell cycle regulation and its molecular implementations, protein number regulation, and population growth, all in relation to size regulation. Finally, we discuss several future directions for developing understanding beyond phenomenological models of cell size regulation.
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Macroscopic Theory for Evolving Biological Systems Akin to Thermodynamics
Vol. 47 (2018), pp. 273–290More LessWe present a macroscopic theory to characterize the plasticity, robustness, and evolvability of biological responses and their fluctuations. First, linear approximation in intracellular reaction dynamics is used to demonstrate proportional changes in the expression of all cellular components in response to a given environmental stress, with the proportion coefficient determined by the change in growth rate as a consequence of the steady growth of cells. We further demonstrate that this relationship is supported through adaptation experiments of bacteria, perhaps too well as this proportionality is held even across cultures of different types of conditions. On the basis of simulations of cell models, we further show that this global proportionality is a consequence of evolution in which expression changes in response to environmental or genetic perturbations are constrained along a unique one-dimensional curve, which is a result of evolutionary robustness. It then follows that the expression changes induced by environmental changes are proportionally reduced across different components of a cell by evolution, which is akin to the Le Chatelier thermodynamics principle. Finally, with the aid of a fluctuation-response relationship, this proportionality is shown to hold between fluctuations caused by genetic changes and those caused by noise. Overall, these results and support from the theoretical and experimental literature suggest a formulation of cellular systems akin to thermodynamics, in which a macroscopic potential is given by the growth rate (or fitness) represented as a function of environmental and evolutionary changes.
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Photoreceptors Take Charge: Emerging Principles for Light Sensing
Vol. 47 (2018), pp. 291–313More LessThe first stage in biological signaling is based on changes in the functional state of a receptor protein triggered by interaction of the receptor with its ligand(s). The light-triggered nature of photoreceptors allows studies on the mechanism of such changes in receptor proteins using a wide range of biophysical methods and with superb time resolution. Here, we critically evaluate current understanding of proton and electron transfer in photosensory proteins and their involvement both in primary photochemistry and subsequent processes that lead to the formation of the signaling state. An insight emerging from multiple families of photoreceptors is that ultrafast primary photochemistry is followed by slower proton transfer steps that contribute to triggering large protein conformational changes during signaling state formation. We discuss themes and principles for light sensing shared by the six photoreceptor families: rhodopsins, phytochromes, photoactive yellow proteins, light-oxygen-voltage proteins, blue-light sensors using flavin, and cryptochromes.
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High-Resolution Hydroxyl Radical Protein Footprinting: Biophysics Tool for Drug Discovery
Vol. 47 (2018), pp. 315–333More LessHydroxyl radical footprinting (HRF) of proteins with mass spectrometry (MS) is a widespread approach for assessing protein structure. Hydroxyl radicals react with a wide variety of protein side chains, and the ease with which radicals can be generated (by radiolysis or photolysis) has made the approach popular with many laboratories. As some side chains are less reactive and thus cannot be probed, additional specific and nonspecific labeling reagents have been introduced to extend the approach. At the same time, advances in liquid chromatography and MS approaches permit an examination of the labeling of individual residues, transforming the approach to high resolution. Lastly, advances in understanding of the chemistry of the approach have led to the determination of absolute protein topologies from HRF data. Overall, the technology can provide precise and accurate measures of side-chain solvent accessibility in a wide range of interesting and useful contexts for the study of protein structure and dynamics in both academia and industry.
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Dynamic Neutron Scattering by Biological Systems
Vol. 47 (2018), pp. 335–354More LessDynamic neutron scattering directly probes motions in biological systems on femtosecond to microsecond timescales. When combined with molecular dynamics simulation and normal mode analysis, detailed descriptions of the forms and frequencies of motions can be derived. We examine vibrations in proteins, the temperature dependence of protein motions, and concepts describing the rich variety of motions detectable using neutrons in biological systems at physiological temperatures. New techniques for deriving information on collective motions using coherent scattering are also reviewed.
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Hydrogel-Tissue Chemistry: Principles and Applications
Vol. 47 (2018), pp. 355–376More LessOver the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three-dimensional positioning and/or brain-wide wiring of those very same neurons—even within vertebrate brains. This new approach and its variants, as applied to neuroscience, are beginning to illuminate the fundamental cellular and chemical representations of sensation, cognition, and action. More generally, reimagining metazoans as metareactants—or positionally defined three-dimensional graphs of constituent chemicals made available for ongoing functionalization, transformation, and readout—is stimulating innovation across biology and medicine.
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Serial Femtosecond Crystallography of G Protein–Coupled Receptors
Vol. 47 (2018), pp. 377–397More LessG protein–coupled receptors (GPCRs) represent a large superfamily of membrane proteins that mediate cell signaling and regulate a variety of physiological processes in the human body. Structure-function studies of this superfamily were enabled a decade ago by multiple breakthroughs in technology that included receptor stabilization, crystallization in a membrane environment, and microcrystallography. The recent emergence of X-ray free-electron lasers (XFELs) has further accelerated structural studies of GPCRs and other challenging proteins by overcoming radiation damage and providing access to high-resolution structures and dynamics using micrometer-sized crystals. Here, we summarize key technology advancements and major milestones of GPCR research using XFELs and provide a brief outlook on future developments in the field.
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Understanding Biological Regulation Through Synthetic Biology
Vol. 47 (2018), pp. 399–423More LessEngineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry—biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.
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Distinct Mechanisms of Transcription Initiation by RNA Polymerases I and II
Vol. 47 (2018), pp. 425–446More LessRNA polymerases I and II (Pol I and Pol II) are the eukaryotic enzymes that catalyze DNA-dependent synthesis of ribosomal RNA and messenger RNA, respectively. Recent work shows that the transcribing forms of both enzymes are similar and the fundamental mechanisms of RNA chain elongation are conserved. However, the mechanisms of transcription initiation and its regulation differ between Pol I and Pol II. Recent structural studies of Pol I complexes with transcription initiation factors provided insights into how the polymerase recognizes its specific promoter DNA, how it may open DNA, and how initiation may be regulated. Comparison with the well-studied Pol II initiation system reveals a distinct architecture of the initiation complex and visualizes promoter- and gene-class-specific aspects of transcription initiation. On the basis of new structural studies, we derive a model of the Pol I transcription cycle and provide a molecular movie of Pol I transcription that can be used for teaching.
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Dynamics of Bacterial Gene Regulatory Networks
Vol. 47 (2018), pp. 447–467More LessThe ability of bacterial cells to adjust their gene expression program in response to environmental perturbation is often critical for their survival. Recent experimental advances allowing us to quantitatively record gene expression dynamics in single cells and in populations coupled with mathematical modeling enable mechanistic understanding on how these responses are shaped by the underlying regulatory networks. Here, we review how the combination of local and global factors affect dynamical responses of gene regulatory networks. Our goal is to discuss the general principles that allow extrapolation from a few model bacteria to less understood microbes. We emphasize that, in addition to well-studied effects of network architecture, network dynamics are shaped by global pleiotropic effects and cell physiology.
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Molecular Mechanisms of Fast Neurotransmitter Release
Vol. 47 (2018), pp. 469–497More LessThis review summarizes current knowledge of synaptic proteins that are central to synaptic vesicle fusion in presynaptic active zones, including SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors), synaptotagmin, complexin, Munc18 (mammalian uncoordinated-18), and Munc13 (mammalian uncoordinated-13), and highlights recent insights in the cooperation of these proteins for neurotransmitter release. Structural and functional studies of the synaptic fusion machinery suggest new molecular models of synaptic vesicle priming and Ca2+-triggered fusion. These studies will be a stepping-stone toward answering the question of how the synaptic vesicle fusion machinery achieves such high speed and sensitivity.
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Structure and Immune Recognition of the HIV Glycan Shield
Vol. 47 (2018), pp. 499–523More LessVaccine design efforts against the human immunodeficiency virus (HIV) have been greatly stimulated by the observation that many infected patients eventually develop highly potent broadly neutralizing antibodies (bnAbs). Importantly, these bnAbs have evolved to recognize not only the two protein components of the viral envelope protein (Env) but also the numerous glycans that form a protective barrier on the Env protein. Because Env is heavily glycosylated compared to host glycoproteins, the glycans have become targets for the antibody response. Therefore, considerable efforts have been made in developing and validating biophysical methods to elucidate the complex structure of the Env-spike glycoprotein, with its combination of glycan and protein epitopes. We illustrate here how the application of robust biophysical methods has transformed our understanding of the structure and function of the HIV Env spike and stimulated innovation in vaccine design strategies that takes into account the essential glycan components.
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Substrate-Induced Formation of Ribosomal Decoding Center for Accurate and Rapid Genetic Code Translation
Vol. 47 (2018), pp. 525–548More LessAccurate translation of genetic information is crucial for synthesis of functional proteins in all organisms. We use recent experimental data to discuss how induced fit affects accuracy of initial codon selection on the ribosome by aminoacyl transfer RNA in ternary complex (T3) with elongation factor Tu (EF-Tu) and guanosine-5′-triphosphate (GTP). We define actual accuracy () of a particular protein synthesis system as its current accuracy and the effective selectivity () as in the limit of zero ribosomal binding affinity for T3. Intrinsic selectivity (), defined as the upper thermodynamic limit of , is determined by the free energy difference between near-cognate and cognate T3 in the pre-GTP hydrolysis state on the ribosome. is much larger than , suggesting the possibility of a considerable increase in and at negligible kinetic cost. Induced fit increases and without affecting , and aminoglycoside antibiotics reduce and at unaltered .
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The Biophysics of 3D Cell Migration
Vol. 47 (2018), pp. 549–567More LessThree-dimensional (3D) cell culture systems have gained increasing interest not only for 3D migration studies but also for their use in drug screening, tissue engineering, and ex vivo modeling of metastatic behavior in the field of cancer biology and morphogenesis in the field of developmental biology. The goal of studying cells in a 3D context is to attempt to more faithfully recapitulate the physiological microenvironment of tissues, including mechanical and structural parameters that we envision will reveal more predictive data for development programs and disease states. In this review, we discuss the pros and cons of several well-characterized 3D cell culture systems for performing 3D migration studies. We discuss the intracellular and extracellular signaling mechanisms that govern cell migration. We also describe the mathematical models and relevant assumptions that can be used to describe 3D cell movement.
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Single-Molecule View of Small RNA–Guided Target Search and Recognition
Vol. 47 (2018), pp. 569–593More LessMost everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid–interacting proteins use distinct target search mechanisms. Several proteins achieve that with the help of short RNA strands known as guides. This review focuses on single-molecule advances studying the target search and recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced short palindromic repeats) systems. We discuss different steps involved in search and recognition, from the initial complex prearrangement into the target-search competent state to the final proofreading steps. We focus on target search mechanisms that range from weak interactions, to one- and three-dimensional diffusion, to conformational proofreading. We compare the mechanisms of Argonaute and CRISPR with a well-studied target search system, RecA.
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Behavioral Variability and Phenotypic Diversity in Bacterial Chemotaxis
Vol. 47 (2018), pp. 595–616More LessLiving cells detect and process external signals using signaling pathways that are affected by random fluctuations. These variations cause the behavior of individual cells to fluctuate over time (behavioral variability) and generate phenotypic differences between genetically identical individuals (phenotypic diversity). These two noise sources reduce our ability to predict biological behavior because they diversify cellular responses to identical signals. Here, we review recent experimental and theoretical advances in understanding the mechanistic origin and functional consequences of such variation in Escherichia coli chemotaxis—a well-understood model of signal transduction and behavior. After briefly summarizing the architecture and logic of the chemotaxis system, we discuss determinants of behavior and chemotactic performance of individual cells. Then, we review how cell-to-cell differences in protein abundance map onto differences in individual chemotactic abilities and how phenotypic variability affects the performance of the population. We conclude with open questions to be addressed by future research.
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Mechanotransduction by the Actin Cytoskeleton: Converting Mechanical Stimuli into Biochemical Signals
Vol. 47 (2018), pp. 617–631More LessForce transmission through the actin cytoskeleton plays a central role in cell movements, shape change, and internal organization. Dynamic reorganization of actin filaments by an array of specialized binding proteins creates biochemically and architecturally distinct structures, many of which are finely tuned to exert or resist mechanical loads. The molecular complexity of the actin cytoskeleton continues to be revealed by detailed biochemical assays, and the architectural diversity and dynamics of actin structures are being uncovered by advances in super-resolution fluorescence microscopy and electron microscopy. However, our understanding of how mechanical forces feed back on cytoskeletal architecture and actin-binding protein organization is comparatively limited. In this review, we discuss recent work investigating how mechanical forces applied to cytoskeletal proteins are transduced into biochemical signals. We explore multiple mechanisms for mechanical signal transduction, including the mechanosensitive behavior of actin-binding proteins, the effect of mechanical force on actin filament dynamics, and the influence of mechanical forces on the structure of single actin filaments. The emerging picture is one in which the actin cytoskeleton is defined not only by the set of proteins that constitute a network but also by the constant interplay of mechanical forces and biochemistry.
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The Physical Properties of Ceramides in Membranes
Vol. 47 (2018), pp. 633–654More LessCeramides are sphingolipids containing a sphingosine or a related base, to which a fatty acid is linked through an amide bond. When incorporated into a lipid bilayer, ceramides exhibit a number of properties not shared by almost any other membrane lipid: Ceramides (a) are extremely hydrophobic and thus cannot exist in suspension in aqueous media; (b) increase the molecular order (rigidity) of phospholipids in membranes; (c) give rise to lateral phase separation and domain formation in phospholipid bilayers; (d) possess a marked intrinsic negative curvature that facilitates formation of inverted hexagonal phases; (e) make bilayers and cell membranes permeable to small and large (i.e., protein-size) solutes; and (f) promote transmembrane (flip-flop) lipid motion. Unfortunately, there is hardly any link between the physical studies reviewed here and the mass of biological and clinical studies on the effects of ceramides in health and disease.
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The Physics of the Metaphase Spindle
Vol. 47 (2018), pp. 655–673More LessThe assembly of the mitotic spindle and the subsequent segregation of sister chromatids are based on the self-organized action of microtubule filaments, motor proteins, and other microtubule-associated proteins, which constitute the fundamental force-generating elements in the system. Many of the components in the spindle have been identified, but until recently it remained unclear how their collective behaviors resulted in such a robust bipolar structure. Here, we review the current understanding of the physics of the metaphase spindle that is only now starting to emerge.
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Previous Volumes
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Volume 52 (2023)
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Volume 51 (2022)
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Volume 50 (2021)
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Volume 49 (2020)
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Volume 48 (2019)
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Volume 47 (2018)
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Volume 46 (2017)
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Volume 45 (2016)
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Volume 44 (2015)
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Volume 43 (2014)
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Volume 42 (2013)
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Volume 41 (2012)
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Volume 40 (2011)
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Volume 39 (2010)
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Volume 38 (2009)
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Volume 37 (2008)
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Volume 36 (2007)
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Volume 35 (2006)
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Volume 34 (2005)
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Volume 33 (2004)
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Volume 32 (2003)
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Volume 31 (2002)
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Volume 30 (2001)
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Volume 29 (2000)
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Volume 28 (1999)
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Volume 27 (1998)
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Volume 26 (1997)
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Volume 25 (1996)
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Volume 24 (1995)
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Volume 23 (1994)
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Volume 22 (1993)
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Volume 21 (1992)
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Volume 20 (1991)
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Volume 19 (1990)
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Volume 18 (1989)
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Volume 17 (1988)
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Volume 16 (1987)
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Volume 15 (1986)
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Volume 14 (1985)
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Volume 13 (1984)
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Volume 12 (1983)
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Volume 11 (1982)
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Volume 10 (1981)
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Volume 9 (1980)
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Volume 8 (1979)
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Volume 7 (1978)
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Volume 6 (1977)
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Volume 5 (1976)
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Volume 4 (1975)
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Volume 3 (1974)
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Volume 2 (1973)
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Volume 1 (1972)
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Volume 0 (1932)