332 results match your criteria Annual Review of Biophysics[Journal]


The Effects of Temperature on Cellular Physiology.

Annu Rev Biophys 2022 May;51:499-526

Biophysics Program, Stanford University School of Medicine, Stanford, California, USA; email:

Temperature impacts biological systems across all length and timescales. Cells and the enzymes that comprise them respond to temperature fluctuations on short timescales, and temperature can affect protein folding, the molecular composition of cells, and volume expansion. Entire ecosystems exhibit temperature-dependent behaviors, and global warming threatens to disrupt thermal homeostasis in microbes that are important for human and planetary health. Read More

View Article and Full-Text PDF

Macromolecular Crowding Is More than Hard-Core Repulsions.

Annu Rev Biophys 2022 May 3;51:267-300. Epub 2022 Mar 3.

Department of Chemistry, University of North Carolina at Chapel Hill, North Carolina, USA; email:

Cells are crowded, but proteins are almost always studied in dilute aqueous buffer. We review the experimental evidence that crowding affects the equilibrium thermodynamics of protein stability and protein association and discuss the theories employed to explain these observations. In doing so, we highlight differences between synthetic polymers and biologically relevant crowders. Read More

View Article and Full-Text PDF

Molecular Shape Solution for Mesoscopic Remodeling of Cellular Membranes.

Annu Rev Biophys 2022 May 3;51:473-497. Epub 2022 Mar 3.

Biofisika Institute (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa, Spain; email:

Cellular membranes self-assemble from and interact with various molecular species. Each molecule locally shapes the lipid bilayer, the soft elastic core of cellular membranes. The dynamic architecture of intracellular membrane systems is based on elastic transformations and lateral redistribution of these elementary shapes, driven by chemical and curvature stress gradients. Read More

View Article and Full-Text PDF

Molecular Mechanisms Underlying Neurotransmitter Release.

Authors:
Josep Rizo

Annu Rev Biophys 2022 May 15;51:377-408. Epub 2022 Feb 15.

Departments of Biophysics, Biochemistry, and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA; email:

Major recent advances and previous data have led to a plausible model of how key proteins mediate neurotransmitter release. In this model, the soluble -ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE) proteins syntaxin-1, SNAP-25, and synaptobrevin form tight complexes that bring the membranes together and are crucial for membrane fusion. NSF and SNAPs disassemble SNARE complexes and ensure that fusion occurs through an exquisitely regulated pathway that starts with Munc18-1 bound to a closed conformation of syntaxin-1. Read More

View Article and Full-Text PDF

ATP-Independent Chaperones.

Annu Rev Biophys 2022 May 15;51:409-429. Epub 2022 Feb 15.

Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA; email:

The folding of proteins into their native structure is crucial for the functioning of all biological processes. Molecular chaperones are guardians of the proteome that assist in protein folding and prevent the accumulation of aberrant protein conformations that can lead to proteotoxicity. ATP-independent chaperones do not require ATP to regulate their functional cycle. Read More

View Article and Full-Text PDF

Insights into the Thermodynamics and Kinetics of Amino-Acid Radicals in Proteins.

Authors:
Cecilia Tommos

Annu Rev Biophys 2022 May 8;51:453-471. Epub 2022 Feb 8.

Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA; email:

Some oxidoreductase enzymes use redox-active tyrosine, tryptophan, cysteine, and/or glycine residues as one-electron, high-potential redox (radical) cofactors. Amino-acid radical cofactors typically perform one of four tasks-they work in concert with a metallocofactor to carry out a multielectron redox process, serve as storage sites for oxidizing equivalents, activate the substrate molecules, or move oxidizing equivalents over long distances. It is challenging to experimentally resolve the thermodynamic and kinetic redox properties of a single-amino-acid residue. Read More

View Article and Full-Text PDF

Orientation of Cell Polarity by Chemical Gradients.

Annu Rev Biophys 2022 May 7;51:431-451. Epub 2022 Feb 7.

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA; email:

Accurate decoding of spatial chemical landscapes is critical for many cell functions. Eukaryotic cells decode local chemical gradients to orient growth or movement in productive directions. Recent work on yeast model systems, whose gradient sensing pathways display much less complexity than those in animal cells, has suggested new paradigms for how these very small cells successfully exploit information in noisy and dynamic pheromone gradients to identify their mates. Read More

View Article and Full-Text PDF

Rules of Physical Mathematics Govern Intrinsically Disordered Proteins.

Annu Rev Biophys 2022 May 4;51:355-376. Epub 2022 Feb 4.

Molecular and Cellular Biophysics Program, University of Denver, Denver, Colorado, USA.

In stark contrast to foldable proteins with a unique folded state, intrinsically disordered proteins and regions (IDPs) persist in perpetually disordered ensembles. Yet an IDP ensemble has conformational features-even when averaged-that are specific to its sequence. In fact, subtle changes in an IDP sequence can modulate its conformational features and its function. Read More

View Article and Full-Text PDF

Super-Resolution Microscopy for Structural Cell Biology.

Annu Rev Biophys 2022 May 4;51:301-326. Epub 2022 Feb 4.

Cell Biology & Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany; email:

Super-resolution microscopy techniques, and specifically single-molecule localization microscopy (SMLM), are approaching nanometer resolution inside cells and thus have great potential to complement structural biology techniques such as electron microscopy for structural cell biology. In this review, we introduce the different flavors of super-resolution microscopy, with a special emphasis on SMLM and MINFLUX (minimal photon flux). We summarize recent technical developments that pushed these localization-based techniques to structural scales and review the experimental conditions that are key to obtaining data of the highest quality. Read More

View Article and Full-Text PDF

Waves in Embryonic Development.

Annu Rev Biophys 2022 May 4;51:327-353. Epub 2022 Feb 4.

Laboratoire de physique de l'École Normale Supérieure, CNRS, PSL Research University, Sorbonne Université, Paris, France; email:

Embryonic development hinges on effective coordination of molecular events across space and time. Waves have recently emerged as constituting an ubiquitous mechanism that ensures rapid spreading of regulatory signals across embryos, as well as reliable control of their patterning, namely, for the emergence of body plan structures. In this article, we review a selection of recent quantitative work on signaling waves and present an overview of the theory of waves. Read More

View Article and Full-Text PDF

Morphology and Transport in Eukaryotic Cells.

Annu Rev Biophys 2022 May 19;51:247-266. Epub 2022 Jan 19.

Department of Physics, University of California, San Diego, La Jolla, California, USA; email:

Transport of intracellular components relies on a variety of active and passive mechanisms, ranging from the diffusive spreading of small molecules over short distances to motor-driven motion across long distances. The cell-scale behavior of these mechanisms is fundamentally dependent on the morphology of the underlying cellular structures. Diffusion-limited reaction times can be qualitatively altered by the presence of occluding barriers or by confinement in complex architectures, such as those of reticulated organelles. Read More

View Article and Full-Text PDF

Large Chaperone Complexes Through the Lens of Nuclear Magnetic Resonance Spectroscopy.

Annu Rev Biophys 2022 May 19;51:223-246. Epub 2022 Jan 19.

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA; email:

Molecular chaperones are the guardians of the proteome inside the cell. Chaperones recognize and bind unfolded or misfolded substrates, thereby preventing further aggregation; promoting correct protein folding; and, in some instances, even disaggregating already formed aggregates. Chaperones perform their function by means of an array of weak protein-protein interactions that take place over a wide range of timescales and are therefore invisible to structural techniques dependent upon the availability of highly homogeneous samples. Read More

View Article and Full-Text PDF

Nanomechanics of Blood Clot and Thrombus Formation.

Annu Rev Biophys 2022 May 6;51:201-221. Epub 2022 Jan 6.

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; email:

Mechanical properties have been extensively studied in pure elastic or viscous materials; however, most biomaterials possess both physical properties in a viscoelastic component. How the biomechanics of a fibrin clot is related to its composition and the microenvironment where it is formed is not yet fully understood. This review gives an outline of the building mechanisms for blood clot mechanical properties and how they relate to clot function. Read More

View Article and Full-Text PDF

Protein Sequencing, One Molecule at a Time.

Annu Rev Biophys 2022 May 5;51:181-200. Epub 2022 Jan 5.

Department of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, Texas, USA; email:

Despite tremendous gains over the past decade, methods for characterizing proteins have generally lagged behind those for nucleic acids, which are characterized by extremely high sensitivity, dynamic range, and throughput. However, the ability to directly characterize proteins at nucleic acid levels would address critical biological challenges such as more sensitive medical diagnostics, deeper protein quantification, large-scale measurement, and discovery of alternate protein isoforms and modifications and would open new paths to single-cell proteomics. In response to this need, there has been a push to radically improve protein sequencing technologies by taking inspiration from high-throughput nucleic acid sequencing, with a particular focus on developing practical methods for single-molecule protein sequencing (SMPS). Read More

View Article and Full-Text PDF

Native Mass Spectrometry: Recent Progress and Remaining Challenges.

Annu Rev Biophys 2022 May 4;51:157-179. Epub 2022 Jan 4.

Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA; email:

Native mass spectrometry (nMS) has emerged as an important tool in studying the structure and function of macromolecules and their complexes in the gas phase. In this review, we cover recent advances in nMS and related techniques including sample preparation, instrumentation, activation methods, and data analysis software. These advances have enabled nMS-based techniques to address a variety of challenging questions in structural biology. Read More

View Article and Full-Text PDF

Chaperonin Mechanisms: Multiple and (Mis)Understood?

Annu Rev Biophys 2022 May 4;51:115-133. Epub 2022 Jan 4.

Department of Macromolecular Structure, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain; email:

The chaperonins are ubiquitous and essential nanomachines that assist in protein folding in an ATP-driven manner. They consist of two back-to-back stacked oligomeric rings with cavities in which protein (un)folding can take place in a shielding environment. This review focuses on GroEL from and the eukaryotic chaperonin-containing t-complex polypeptide 1, which differ considerably in their reaction mechanisms despite sharing a similar overall architecture. Read More

View Article and Full-Text PDF

Lipid-Protein Interactions in Plasma Membrane Organization and Function.

Annu Rev Biophys 2022 May 4;51:135-156. Epub 2022 Jan 4.

Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden; email:

Lipid-protein interactions in cells are involved in various biological processes, including metabolism, trafficking, signaling, host-pathogen interactions, and transmembrane transport. At the plasma membrane, lipid-protein interactions play major roles in membrane organization and function. Several membrane proteins have motifs for specific lipid binding, which modulate protein conformation and consequent function. Read More

View Article and Full-Text PDF

Phospholipid Scrambling by G Protein-Coupled Receptors.

Annu Rev Biophys 2022 May 21;51:39-61. Epub 2021 Dec 21.

Department of Biochemistry, Weill Cornell Medical College, New York, New York, USA; email:

Rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. The transport proteins that facilitate this process are classified as pump-like flippases and floppases and channel-like scramblases. Unexpectedly, Class A G protein-coupled receptors (GPCRs), a large class of signaling proteins exemplified by the visual receptor rhodopsin and its apoprotein opsin, are constitutively active as scramblases in vitro. Read More

View Article and Full-Text PDF

Enzymology and Dynamics by Cryogenic Electron Microscopy.

Annu Rev Biophys 2022 May 21;51:19-38. Epub 2021 Dec 21.

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; email:

Cryogenic electron microscopy (cryo-EM) has revolutionized the field of structural biology, particularly in solving the structures of large protein complexes or cellular machineries that play important biological functions. This review focuses on the contribution and future potential of cryo-EM in related emerging applications-enzymatic mechanisms and dynamic processes. Work on these subjects can benefit greatly from the capability of cryo-EM to solve the structures of specific protein complexes in multiple conditions, including variations in the buffer condition, ligands, and temperature, and to capture multiple conformational states, conformational change intermediates, and reaction intermediates. Read More

View Article and Full-Text PDF

Chiral Induced Spin Selectivity and Its Implications for Biological Functions.

Annu Rev Biophys 2022 May 21;51:99-114. Epub 2021 Dec 21.

Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; email:

Chirality in life has been preserved throughout evolution. It has been assumed that the main function of chirality is its contribution to structural properties. In the past two decades, however, it has been established that chiral molecules possess unique electronic properties. Read More

View Article and Full-Text PDF

Variable-Temperature Native Mass Spectrometry for Studies of Protein Folding, Stabilities, Assembly, and Molecular Interactions.

Annu Rev Biophys 2022 May 21;51:63-77. Epub 2021 Dec 21.

Department of Chemistry, Texas A&M University, College Station, Texas, USA; email:

The structures and conformational dynamics of proteins, protein complexes, and their noncovalent interactions with other molecules are controlled specifically by the Gibbs free energy (entropy and enthalpy) of the system. For some organisms, temperature is highly regulated, but the majority of biophysical studies are carried out at room, nonphysiological temperature. In this review, we describe variable-temperature electrospray ionization (vT-ESI) mass spectrometry (MS)-based studies with unparalleled sensitivity, dynamic range, and selectivity for studies of both cold- and heat-induced chemical processes. Read More

View Article and Full-Text PDF

A Life of Biophysics.

Authors:
Bertil Hille

Annu Rev Biophys 2022 May 21;51:1-17. Epub 2021 Dec 21.

Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington, USA; email:

Biophysics is a way of approaching biological problems through numbers, physical laws, models, and quantitative logic. In a long scientific career, I have seen the formation and fruition of the ion channel concept through biophysical study. Marvelous discoveries were made as our instruments evolved from vacuum tubes to transistors; computers evolved from the size of an entire building to a few chips inside our instruments; and genome sequencing, gene expression, and atom-level structural biology became accessible to all laboratories. Read More

View Article and Full-Text PDF

Mapping Enzyme Landscapes by Time-Resolved Crystallography with Synchrotron and X-Ray Free Electron Laser Light.

Authors:
Mark A Wilson

Annu Rev Biophys 2022 May 21;51:79-98. Epub 2021 Dec 21.

Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, Nebraska, USA; email:

Directly observing enzyme catalysis in real time at the molecular level has been a long-standing goal of structural enzymology. Time-resolved serial crystallography methods at synchrotron and X-ray free electron laser (XFEL) sources have enabled researchers to follow enzyme catalysis and other nonequilibrium events at ambient conditions with unprecedented time resolution. X-ray crystallography provides detailed information about conformational heterogeneity and protein dynamics, which is enhanced when time-resolved approaches are used. Read More

View Article and Full-Text PDF

The Contribution of Biophysics and Structural Biology to Current Advances in COVID-19.

Annu Rev Biophys 2021 05;50:493-523

Biomedical Research Institute (BIOMED), Catholic University of Argentina (UCA)-National Scientific and Technical Research Council, Argentina (CONICET), C1107AFF Buenos Aires, Argentina; email:

Critical to viral infection are the multiple interactions between viral proteins and host-cell counterparts. The first such interaction is the recognition of viral envelope proteins by surface receptors that normally fulfil other physiological roles, a hijacking mechanism perfected over the course of evolution. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), has successfully adopted this strategy using its spike glycoprotein to dock on the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2). Read More

View Article and Full-Text PDF

Structure and Mechanics of Dynein Motors.

Annu Rev Biophys 2021 05;50:549-574

Biophysics Graduate Group, University of California, Berkeley, California 94720, USA; email:

Dyneins make up a family of AAA+ motors that move toward the minus end of microtubules. Cytoplasmic dynein is responsible for transporting intracellular cargos in interphase cells and mediating spindle assembly and chromosome positioning during cell division. Other dynein isoforms transport cargos in cilia and power ciliary beating. Read More

View Article and Full-Text PDF

The Phasor Plot: A Universal Circle to Advance Fluorescence Lifetime Analysis and Interpretation.

Annu Rev Biophys 2021 05;50:575-593

Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, California 92697, USA; email:

The phasor approach to fluorescence lifetime imaging has become a common method to analyze complicated fluorescence signals from biological samples. The appeal of the phasor representation of complex fluorescence decays in biological systems is that a visual representation of the decay of entire cells or tissues can be used to easily interpret fundamental biological states related to metabolism and oxidative stress. Phenotyping based on autofluorescence provides new avenues for disease characterization and diagnostics. Read More

View Article and Full-Text PDF

Structure of Phycobilisomes.

Authors:
Sen-Fang Sui

Annu Rev Biophys 2021 05;50:53-72

State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology and Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China; email:

Phycobilisomes (PBSs) are extremely large chromophore-protein complexes on the stromal side of the thylakoid membrane in cyanobacteria and red algae. The main function of PBSs is light harvesting, and they serve as antennas and transfer the absorbed energy to the reaction centers of two photosynthetic systems (photosystems I and II). PBSs are composed of phycobiliproteins and linker proteins. Read More

View Article and Full-Text PDF

Structures and Functions of Chromatin Fibers.

Annu Rev Biophys 2021 05;50:95-116

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; email:

In eukaryotes, genomic DNA is packaged into chromatin in the nucleus. The accessibility of DNA is dependent on the chromatin structure and dynamics, which essentially control DNA-related processes, including transcription, DNA replication, and repair. All of the factors that affect the structure and dynamics of nucleosomes, the nucleosome-nucleosome interaction interfaces, and the binding of linker histones or other chromatin-binding proteins need to be considered to understand the organization and function of chromatin fibers. Read More

View Article and Full-Text PDF

From Bench to Keyboard and Back Again: A Brief History of Lambda Phage Modeling.

Annu Rev Biophys 2021 05;50:117-134

The Louis and Beatrice Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, New York 11794, USA; email:

Cellular decision making is the process whereby cells choose one developmental pathway from multiple possible ones, either spontaneously or due to environmental stimuli. Examples in various cell types suggest an almost inexhaustible plethora of underlying molecular mechanisms. In general, cellular decisions rely on the gene regulatory network, which integrates external signals to drive cell fate choice. Read More

View Article and Full-Text PDF

Molecular Force Measurement with Tension Sensors.

Annu Rev Biophys 2021 05 12;50:595-616. Epub 2021 Mar 12.

Department of Quantitative Cell Biology, Institute of Molecular Cell Biology, University of Münster, Münster D-48149, Germany; email:

The ability of cells to generate mechanical forces, but also to sense, adapt to, and respond to mechanical signals, is crucial for many developmental, postnatal homeostatic, and pathophysiological processes. However, the molecular mechanisms underlying cellular mechanotransduction have remained elusive for many decades, as techniques to visualize and quantify molecular forces across individual proteins in cells were missing. The development of genetically encoded molecular tension sensors now allows the quantification of piconewton-scale forces that act upon distinct molecules in living cells and even whole organisms. Read More

View Article and Full-Text PDF