{"title":"Mitochondrial Outer Membrane Voltage-Dependent Anion Channels: Unique Structures, Distinct Functions, and Novel Therapeutic Targets.","authors":"Shashank Ranjan Srivastava, Aadish Rawat, Radhakrishnan Mahalakshmi","doi":"10.1146/annurev-biophys-061124-102155","DOIUrl":"10.1146/annurev-biophys-061124-102155","url":null,"abstract":"<p><p>Voltage-dependent anion channels (VDACs) of the outer mitochondrial membrane carry out bidirectional flux of metabolites and ions and serve as the first line of communication between the cytosol and mitochondria. They are now recognized as indispensable for mitochondrial function and cellular homeostasis, mitochondria-endoplasmic reticulum communication, lipid and cholesterol biogenesis, Ca2+ homeostasis, and mitochondria-mediated apoptosis. The unique structural features of VDACs are also important in redox regulation. VDAC dysregulation by interaction with amyloid-β, α-synuclein, Tau, or tubulin can lead to neurodegeneration. Here, we provide insights into the structures, isoform-specific molecular functions, cellular interactome, variations, and unique regulatory elements of VDACs and their direct implications for widespread burdens like cancer and neurodegeneration in humans. We discuss how deducing isoform-specific structure-function studies of VDACs has the potential for successful development of next-generation diagnostics-guided therapeutics.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":"391-414"},"PeriodicalIF":12.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual Review of BiophysicsPub Date : 2026-05-01Epub Date: 2026-01-20DOI: 10.1146/annurev-biophys-030822-031838
Kaushik Roy, Aryeh Warmflash
{"title":"Pattern Formation in Cell Cultures.","authors":"Kaushik Roy, Aryeh Warmflash","doi":"10.1146/annurev-biophys-030822-031838","DOIUrl":"10.1146/annurev-biophys-030822-031838","url":null,"abstract":"<p><p>Pattern formation, or the emergence of spatial order and fate specification from initially homogeneous cell populations, is a fundamental problem in developmental biology and biophysics. In vitro cell culture platforms now provide powerful tools to investigate the mechanisms of pattern formation under controlled conditions. In this review, we present an integrated perspective on recent advances in pattern formation studies across a diverse array of in vitro systems, organized thematically by the experimental platforms they employ and the underlying principles they reveal, ranging from biochemical gradients to dynamic signaling and mechanochemical feedback. We discuss how these systems recapitulate principles such as morphogen gradients and reaction-diffusion dynamics while enabling mechanistic dissection of self-organization. Particular emphasis is placed on stem cell-based models of early human development that provide unique access to early developmental patterning. We further explore how dynamic signaling, collective behavior, and multisignal integration define emergent patterning phenomena. Finally, we outline future challenges and opportunities in combining theoretical and experimental approaches to model and engineer spatial organization in multicellular systems.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":"199-224"},"PeriodicalIF":12.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual Review of BiophysicsPub Date : 2026-05-01Epub Date: 2026-01-02DOI: 10.1146/annurev-biophys-021424-124520
Ken Halvorsen, Andrew Ward, Wesley P Wong
{"title":"Beyond the Single Molecule: Multiplexed Methods in Force Spectroscopy.","authors":"Ken Halvorsen, Andrew Ward, Wesley P Wong","doi":"10.1146/annurev-biophys-021424-124520","DOIUrl":"10.1146/annurev-biophys-021424-124520","url":null,"abstract":"<p><p>Single-molecule techniques have transformed biological research by enabling direct observation and manipulation of individual molecules. These methods overcome ensemble averaging inherent in bulk measurements and facilitate studies under physiological stresses and out-of-equilibrium conditions. They have provided valuable insights into diverse biological processes, from stepping mechanisms of molecular motors to mechanical properties of biomolecules to the dynamic strength of intermolecular bonds. Advances in multiplexed and high-throughput single-molecule force spectroscopy methods are improving throughput, capabilities, and accessibility. In this review, we detail the evolution of multiplexed force spectroscopy technologies, highlighting key advances in instrumentation, molecular engineering, and analytical techniques. We discuss diverse applications spanning molecular biophysics, biomolecular sensing, proteomics, and cellular mechanobiology. Finally, we explore ongoing challenges and future opportunities and highlight how the impact of multiplexed single-molecule force spectroscopy can continue to grow through further developments in novel instrumentation, chemical tools, and innovative applications.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":"135-155"},"PeriodicalIF":12.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bioenergetics and the Evolution of Cellular Traits.","authors":"Paul E Schavemaker, Michael Lynch","doi":"10.1146/annurev-biophys-070524-090334","DOIUrl":"10.1146/annurev-biophys-070524-090334","url":null,"abstract":"<p><p>Evolutionary processes have transformed simple cellular life into a great diversity of forms, ranging from the ubiquitous eukaryotic cell design to the more specific cellular forms of spirochetes, cyanobacteria, ciliates, heliozoans, amoeba, and many others. The cellular traits that constitute these forms require an evolutionary explanation. Ultimately, the persistence of a cellular trait depends on its net contribution to fitness, a quantitative measure. Independent of any positive effects, a cellular trait exhibits a baseline energetic cost that needs to be accounted for when quantitatively examining its net fitness effect. Here, we explore how the energetic burden introduced by a cellular trait quantitatively affects cellular fitness, describe methods for determining cell energy budgets, summarize the costs of cellular traits across the tree of life, and examine how the fitness impacts of these energetic costs compare to other evolutionary forces and trait benefits.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":"54 1","pages":"81-99"},"PeriodicalIF":12.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual Review of BiophysicsPub Date : 2025-05-01Epub Date: 2024-12-17DOI: 10.1146/annurev-biophys-080124-123012
Tobin R Sosnick, Michael C Baxa
{"title":"Collapse and Protein Folding: Should We Be Surprised That Biothermodynamics Works So Well?","authors":"Tobin R Sosnick, Michael C Baxa","doi":"10.1146/annurev-biophys-080124-123012","DOIUrl":"10.1146/annurev-biophys-080124-123012","url":null,"abstract":"<p><p>A complete understanding of protein function and dynamics requires the characterization of the multiple thermodynamic states, including the denatured state ensemble (DSE). Whereas residual structure in the DSE (as well as in partially folded states) is pertinent in many biological contexts, here we are interested in how such structure affects protein thermodynamics. We examine issues related to chain collapse in light of new developments, focusing on potential complications arising from differences in the DSE's properties under various conditions. Despite some variability in the degree of collapse and structure in the DSE, stability measurements are remarkably consistent between two standard methods, calorimetry and chemical denaturation, as well as with hydrogen-deuterium exchange. This robustness is due in part to the DSEs obtained with different perturbations being thermodynamically equivalent and hence able to serve as a common reference state. An examination of the properties of the DSE points to it as being a highly expanded ensemble with minimal amounts of stable hydrogen bonded structure. These two features are likely to be critical in the broad and successful application of thermodynamics to protein folding. Our review concludes with a discussion of the impact of these findings on folding mechanisms and pathways.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":"17-34"},"PeriodicalIF":13.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Physics of Sensing and Decision-Making by Animal Groups.","authors":"Danielle L Chase, Orit Peleg","doi":"10.1146/annurev-biophys-061824-110733","DOIUrl":"10.1146/annurev-biophys-061824-110733","url":null,"abstract":"<p><p>To ensure survival and reproduction, individual animals navigating the world must regularly sense their surroundings and use this information for important decision-making. The same is true for animals living in groups, where the roles of sensing, information propagation, and decision-making are distributed on the basis of individual knowledge, spatial position within the group, and more. This review highlights key examples of temporal and spatiotemporal dynamics in animal group decision-making, emphasizing strong connections between mathematical models and experimental observations. We start with models of temporal dynamics, such as reaching consensus and the time dynamics of excitation-inhibition networks. For spatiotemporal dynamics in sparse groups, we explore the propagation of information and synchronization of movement in animal groups with models of self-propelled particles, where interactions are typically parameterized by length and timescales. In dense groups, we examine crowding effects using a soft condensed matter approach, where interactions are parameterized by physical potentials and forces. While focusing on invertebrates, we also demonstrate the applicability of these results to a wide range of organisms, aiming to provide an overview of group behavior dynamics and identify new areas for exploration.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":"54 1","pages":"329-351"},"PeriodicalIF":13.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual Review of BiophysicsPub Date : 2025-05-01Epub Date: 2025-02-14DOI: 10.1146/annurev-biophys-030722-110624
Suman Kulkarni, Dani S Bassett
{"title":"Toward Principles of Brain Network Organization and Function.","authors":"Suman Kulkarni, Dani S Bassett","doi":"10.1146/annurev-biophys-030722-110624","DOIUrl":"10.1146/annurev-biophys-030722-110624","url":null,"abstract":"<p><p>The brain is immensely complex, with diverse components and dynamic interactions building upon one another to orchestrate a wide range of behaviors. Understanding patterns of these complex interactions and how they are coordinated to support collective neural function is critical for parsing human and animal behavior, treating mental illness, and developing artificial intelligence. Rapid experimental advances in imaging, recording, and perturbing neural systems across various species now provide opportunities to distill underlying principles of brain organization and function. Here, we take stock of recent progress and review methods used in the statistical analysis of brain networks, drawing from fields of statistical physics, network theory, and information theory. Our discussion is organized by scale, starting with models of individual neurons and extending to large-scale networks mapped across brain regions. We then examine organizing principles and constraints that shape the biological structure and function of neural circuits. We conclude with an overview of several critical frontiers, including expanding current models, fostering tighter feedback between theory and experiment, and leveraging perturbative approaches to understand neural systems. Alongside these efforts, we highlight the importance of contextualizing their contributions by linking them to formal accounts of explanation and causation.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":"353-378"},"PeriodicalIF":13.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Werner Kühlbrandt, Luis A M Carreira, Özkan Yildiz
{"title":"Cryo-EM of Mitochondrial Complex I and ATP Synthase.","authors":"Werner Kühlbrandt, Luis A M Carreira, Özkan Yildiz","doi":"10.1146/annurev-biophys-060724-110838","DOIUrl":"10.1146/annurev-biophys-060724-110838","url":null,"abstract":"<p><p>Cryo-electron microscopy (cryo-EM) is the method of choice for investigating the structures of membrane protein complexes at high resolution under near-native conditions. This review focuses on recent cryo-EM work on mitochondrial complex I and ATP synthase. Single-particle cryo-EM structures of complex I from mammals, plants, and fungi extending to a resolution of 2 Å show different functional states, indicating consistent conformational changes of loops near the Q binding site, clusters of internal water molecules in the membrane arm, and an α-π transition in a membrane-spanning helix that opens and closes the proton transfer path. Cryo-EM structures of ATP synthase dimers from mammalian, yeast, and <i>Polytomella</i> mitochondria show several rotary states at a resolution of 2.7 to 3.5 Å. The new structures of complex I and ATP synthase are important steps along the way toward understanding the detailed molecular mechanisms of both complexes. Cryo-electron tomography and subtomogram averaging have the potential to resolve their high-resolution structures in situ.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":"54 1","pages":"209-226"},"PeriodicalIF":13.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual Review of BiophysicsPub Date : 2025-05-01Epub Date: 2025-01-21DOI: 10.1146/annurev-biophys-070924-103134
Shuobo Shi, Yu Chen, Jens Nielsen
{"title":"Metabolic Engineering of Yeast.","authors":"Shuobo Shi, Yu Chen, Jens Nielsen","doi":"10.1146/annurev-biophys-070924-103134","DOIUrl":"10.1146/annurev-biophys-070924-103134","url":null,"abstract":"<p><p>Microbial cell factories have been developed to produce various compounds in a sustainable and economically viable manner. The yeast <i>Saccharomyces cerevisiae</i> has been used as a platform cell factory in industrial biotechnology with numerous advantages, including ease of operation, rapid growth, and tolerance for various industrial stressors. Advances in synthetic biology and metabolic models have accelerated the design-build-test-learn cycle in metabolic engineering, significantly facilitating the development of yeast strains with complex phenotypes, including the redirection of metabolic fluxes to desired products, the expansion of the spectrum of usable substrates, and the improvement of the physiological properties of strain. Strains with enhanced titer, rate, and yield are now competing with traditional petroleum-based industrial approaches. This review highlights recent advances and perspectives in the metabolic engineering of yeasts for the production of a variety of compounds, including fuels, chemicals, proteins, and peptides, as well as advancements in synthetic biology tools and mathematical modeling.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":"101-120"},"PeriodicalIF":13.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual Review of BiophysicsPub Date : 2025-05-01Epub Date: 2025-02-14DOI: 10.1146/annurev-biophys-070124-092816
Matthew MacAinsh, Fidha Nazreen Kunnath Muhammedkutty, Ramesh Prasad, Huan-Xiang Zhou
{"title":"Membrane Association of Intrinsically Disordered Proteins.","authors":"Matthew MacAinsh, Fidha Nazreen Kunnath Muhammedkutty, Ramesh Prasad, Huan-Xiang Zhou","doi":"10.1146/annurev-biophys-070124-092816","DOIUrl":"10.1146/annurev-biophys-070124-092816","url":null,"abstract":"<p><p>It is now clear that membrane association of intrinsically disordered proteins or intrinsically disordered regions regulates many cellular processes, such as membrane targeting of Src family kinases and ion channel gating. Residue-specific characterization by nuclear magnetic resonance spectroscopy, molecular dynamics simulations, and other techniques has shown that polybasic motifs and amphipathic helices are the main drivers of membrane association; sequence-based prediction of residue-specific membrane association propensity has become possible. Membrane association facilitates protein-protein interactions and protein aggregation-these effects are due to reduced dimensionality but are similar to those afforded by condensate formation via liquid-liquid phase separation (LLPS). LLPS at the membrane surface provides a powerful means for recruiting and clustering proteins, as well as for membrane remodeling.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":"275-302"},"PeriodicalIF":12.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}