Christopher Joel Russo, Kabir Husain, Arvind Murugan
{"title":"Soft Modes as a Predictive Framework for Low-Dimensional Biological Systems Across Scales.","authors":"Christopher Joel Russo, Kabir Husain, Arvind Murugan","doi":"10.1146/annurev-biophys-081624-030543","DOIUrl":"https://doi.org/10.1146/annurev-biophys-081624-030543","url":null,"abstract":"<p><p>All biological systems are subject to perturbations arising from thermal fluctuations, external environments, or mutations. Yet, while biological systems consist of thousands of interacting components, recent high-throughput experiments have shown that their response to perturbations is surprisingly low dimensional: confined to only a few stereotyped changes out of the many possible. In this review, we explore a unifying dynamical systems framework-soft modes-to explain and analyze low dimensionality in biology, from molecules to ecosystems. We argue that this soft mode framework makes nontrivial predictions that generalize classic ideas from developmental biology to disparate systems, namely phenocopying, dual buffering, and global epistasis. While some of these predictions have been borne out in experiments, we discuss how soft modes allow for a surprisingly far-reaching and unifying framework in which to analyze data from protein biophysics to microbial ecology.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460470","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}
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":""},"PeriodicalIF":10.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toward Principles of Brain Network Organization and Function.","authors":"Suman Kulkarni, Dani S Bassett","doi":"10.1146/annurev-biophys-030722-110624","DOIUrl":"https://doi.org/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 the 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":""},"PeriodicalIF":10.4,"publicationDate":"2025-02-14","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}
Niels Radmacher, Alexey I Chizhik, Oleksii Nevskyi, José Ignacio Gallea, Ingo Gregor, Jörg Enderlein
{"title":"Molecular Level Super-Resolution Fluorescence Imaging.","authors":"Niels Radmacher, Alexey I Chizhik, Oleksii Nevskyi, José Ignacio Gallea, Ingo Gregor, Jörg Enderlein","doi":"10.1146/annurev-biophys-071524-105321","DOIUrl":"https://doi.org/10.1146/annurev-biophys-071524-105321","url":null,"abstract":"<p><p>Over the last 30 years, fluorescence microscopy, renowned for its sensitivity and specificity, has undergone a revolution in resolving ever-smaller details. This advancement began with stimulated emission depletion (STED) microscopy and progressed with techniques such as photoactivatable localization microscopy and stochastic optical reconstruction microscopy (STORM). Single-molecule localization microscopy (SMLM), which encompasses methods like direct STORM, has significantly enhanced image resolution. Even though its speed is slower than that of STED, SMLM achieves higher resolution by overcoming photobleaching limitations, particularly through DNA point accumulation for imaging in nanoscale topography (DNA-PAINT), which continuously renews fluorescent labels. Additionally, cryo-fluorescence microscopy and advanced techniques like minimal photon fluxes imaging (MINFLUX) have pushed the boundaries toward molecular resolution SMLM. This review discusses the latest developments in SMLM, highlighting methods like resolution enhancement by sequential imaging (RESI) and PAINT-MINFLUX and exploring axial localization techniques such as supercritical angle fluorescence and metal-induced energy transfer. These advancements promise to revolutionize fluorescence microscopy, providing resolution comparable to that of electron microscopy.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426588","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}
Jiapeng Wei, Georg Meisl, Alexander J Dear, Thomas C T Michaels, Tuomas P J Knowles
{"title":"Kinetics of Amyloid Oligomer Formation.","authors":"Jiapeng Wei, Georg Meisl, Alexander J Dear, Thomas C T Michaels, Tuomas P J Knowles","doi":"10.1146/annurev-biophys-080124-122953","DOIUrl":"https://doi.org/10.1146/annurev-biophys-080124-122953","url":null,"abstract":"<p><p>Low-molecular-weight oligomers formed from amyloidogenic peptides and proteins have been identified as key cytotoxins across a range of neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Developing therapeutic strategies that target oligomers is therefore emerging as a promising approach for combating protein misfolding diseases. As such, there is a great need to understand the fundamental properties, dynamics, and mechanisms associated with oligomer formation. In this review, we discuss how chemical kinetics provides a powerful tool for studying these systems. We review the chemical kinetics approach to determining the underlying molecular pathways of protein aggregation and discuss its applications to oligomer formation and dynamics. We discuss how this approach can reveal detailed mechanisms of primary and secondary oligomer formation, including the role of interfaces in these processes. We further use this framework to describe the processes of oligomer conversion and dissociation, and highlight the distinction between on-pathway and off-pathway oligomers. Furthermore, we showcase on the basis of experimental data the diversity of pathways leading to oligomer formation in various in vitro and in silico systems. Finally, using the lens of the chemical kinetics framework, we look at the current oligomer inhibitor strategies both in vitro and in vivo.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392063","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}
Guillaume Romet-Lemonne, Cécile Leduc, Antoine Jégou, Hugo Wioland
{"title":"Mechanics of Single Cytoskeletal Filaments.","authors":"Guillaume Romet-Lemonne, Cécile Leduc, Antoine Jégou, Hugo Wioland","doi":"10.1146/annurev-biophys-030722-120914","DOIUrl":"https://doi.org/10.1146/annurev-biophys-030722-120914","url":null,"abstract":"<p><p>The cytoskeleton comprises networks of different biopolymers, which serve various cellular functions. To accomplish these tasks, their mechanical properties are of particular importance. Understanding them requires detailed knowledge of the mechanical properties of the individual filaments that make up these networks, in particular, microtubules, actin filaments, and intermediate filaments. Far from being homogeneous beams, cytoskeletal filaments have complex mechanical properties, which are directly related to the specific structural arrangement of their subunits. They are also versatile, as the filaments' mechanics and biochemistry are tightly coupled, and their properties can vary with the cellular context. In this review, we summarize decades of research on cytoskeletal filament mechanics, highlighting their most salient features and discussing recent insights from this active field of research.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392065","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":"Information Processing in Biochemical Networks.","authors":"Gašper Tkačik, Pieter Rein Ten Wolde","doi":"10.1146/annurev-biophys-060524-102720","DOIUrl":"https://doi.org/10.1146/annurev-biophys-060524-102720","url":null,"abstract":"<p><p>Living systems are characterized by controlled flows of matter, energy, and information. While the biophysics community has productively engaged with the first two, addressing information flows has been more challenging, with some scattered success in evolutionary theory and a more coherent track record in neuroscience. Nevertheless, interdisciplinary work of the past two decades at the interface of biophysics, quantitative biology, and engineering has led to an emerging mathematical language for describing information flows at the molecular scale. This is where the central processes of life unfold: from detection and transduction of environmental signals to the readout or copying of genetic information and the triggering of adaptive cellular responses. Such processes are coordinated by complex biochemical reaction networks that operate at room temperature, are out of equilibrium, and use low copy numbers of diverse molecular species with limited interaction specificity. Here we review how flows of information through biochemical networks can be formalized using information-theoretic quantities, quantified from data, and computed within various modeling frameworks. Optimization of information flows is presented as a candidate design principle that navigates the relevant time, energy, crosstalk, and metabolic constraints to predict reliable cellular signaling and gene regulation architectures built of individually noisy components.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391992","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}
Vincent J Hilser, James O Wrabl, Charles E F Millard, Anna Schmitz, Sarah J Brantley, Marie Pearce, Joe Rehfus, Miranda M Russo, Keila Voortman-Sheetz
{"title":"Statistical Thermodynamics of the Protein Ensemble: Mediating Function and Evolution.","authors":"Vincent J Hilser, James O Wrabl, Charles E F Millard, Anna Schmitz, Sarah J Brantley, Marie Pearce, Joe Rehfus, Miranda M Russo, Keila Voortman-Sheetz","doi":"10.1146/annurev-biophys-061824-104900","DOIUrl":"https://doi.org/10.1146/annurev-biophys-061824-104900","url":null,"abstract":"<p><p>The growing appreciation of native state conformational fluctuations mediating protein function calls for critical reevaluation of protein evolution and adaptation. If proteins are ensembles, does nature select solely for ground state structure, or are conformational equilibria between functional states also conserved? If so, what is the mechanism and how can it be measured? Addressing these fundamental questions, we review our investigation into the role of local unfolding fluctuations in the native state ensembles of proteins. We describe the functional importance of these ubiquitous fluctuations, as revealed through studies of adenylate kinase. We then summarize elucidation of thermodynamic organizing principles, which culminate in a quantitative probe for evolutionary conservation of protein energetics. Finally, we show that these principles are predictive of sequence compatibility for multiple folds, providing a unique thermodynamic perspective on metamorphic proteins. These research areas demonstrate that the locally unfolded ensemble is an emerging, important mechanism of protein evolution.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392259","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}
Victor Muñoz, Rama Reddy Goluguri, Catherine Ghosh, Benjamin Tanielian, Mourad Sadqi
{"title":"Mechanisms for DNA Interplay in Eukaryotic Transcription Factors.","authors":"Victor Muñoz, Rama Reddy Goluguri, Catherine Ghosh, Benjamin Tanielian, Mourad Sadqi","doi":"10.1146/annurev-biophys-071524-111008","DOIUrl":"https://doi.org/10.1146/annurev-biophys-071524-111008","url":null,"abstract":"<p><p>Like their prokaryotic counterparts, eukaryotic transcription factors must recognize specific DNA sites, search for them efficiently, and bind to them to help recruit or block the transcription machinery. For eukaryotic factors, however, the genetic signals are extremely complex and scattered over vast, multichromosome genomes, while the DNA interplay occurs in a varying landscape defined by chromatin remodeling events and epigenetic modifications. Eukaryotic factors are rich in intrinsically disordered regions and are also distinct in their recognition of short DNA motifs and utilization of open DNA interaction interfaces as ways to gain access to DNA on nucleosomes. Recent findings are revealing the profound, unforeseen implications of such characteristics for the mechanisms of DNA interplay. In this review we discuss these implications and how they are shaping the eukaryotic transcription control paradigm into one of promiscuous signal recognition, highly dynamic interactions, heterogeneous DNA scanning, and multiprong conformational control.</p>","PeriodicalId":50756,"journal":{"name":"Annual Review of Biophysics","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069306","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":"Metabolic Engineering of Yeast.","authors":"Shuobo Shi, Yu Chen, Jens Nielsen","doi":"10.1146/annurev-biophys-070924-103134","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":10.4,"publicationDate":"2025-01-21","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}