Jacob M Wheelock,Robert Pritchard,Shiv Kumar,Hang Lu
{"title":"Integrative Approaches in Optical Functional Imaging: Optics, Microfluidics, and Machine Learning for Neuroscience in Organoids and Small Animal Models.","authors":"Jacob M Wheelock,Robert Pritchard,Shiv Kumar,Hang Lu","doi":"10.1016/j.bpj.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.015","url":null,"abstract":"Advances in functional imaging have transformed neuroscience, enabling real-time mapping of neural activity and cellular dynamics. Techniques such as light-sheet microscopy allow whole-brain recordings in model organisms like C. elegans and zebrafish, revealing mechanisms of sensorimotor processing, learning, and neural circuit formation. More recently, the vast complexity of these datasets necessitates machine learning tools for efficient analysis. Machine Learning-driven approaches improve data quality through denoising, automate segmentation of neurons and tissues, and enable analyses on complex data. By integrating Machine Learning with advanced imaging, researchers can decode developmental trajectories and neural network function with unprecedented precision. This review explores the synergy between imaging and computation, highlighting how these innovations drive discoveries in neuroscience.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"68 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Electric Fields from Cold Gas Plasmas in Biomedical Applications.","authors":"Sander Bekeschus","doi":"10.1016/j.bpj.2025.09.013","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.013","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"86 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jane Kondev, Marc Kirschner, Hernan G Garcia, Gabriel L Salmon, Rob Phillips
{"title":"Biological processes as exploratory dynamics.","authors":"Jane Kondev, Marc Kirschner, Hernan G Garcia, Gabriel L Salmon, Rob Phillips","doi":"10.1016/j.bpj.2025.09.009","DOIUrl":"10.1016/j.bpj.2025.09.009","url":null,"abstract":"<p><p>Many biological processes can be thought of as the result of an underlying dynamics in which the system repeatedly undergoes distinct and abortive trajectories with the dynamical process only ending when some specific process, purpose, structure, or function is achieved. A classic example is the way in which microtubules attach to kinetochores as a prerequisite for chromosome segregation and cell division. In this example, the dynamics is characterized by apparently futile time histories in which microtubules repeatedly grow and shrink without chromosomal attachment. We hypothesize that for biological processes for which it is not the initial conditions that matter, but rather the final state, this kind of exploratory dynamics is biology's unique and necessary solution to achieving these functions with high fidelity. This kind of cause-and-effect relationship can be contrasted to examples from physics and chemistry where the initial conditions determine the outcome. In this paper, we examine the similarities of many biological processes that depend upon random trajectories starting from the initial state and the selection of subsets of these trajectories to achieve some desired functional final state. We begin by reviewing the long history of the principles of dynamics, first in the context of physics, and then in the context of the study of life. These ideas are then stacked up against the broad categories of biological phenomenology that exhibit exploratory dynamics. We then build on earlier work by making a quantitative examination of a succession of increasingly sophisticated models for exploratory dynamics, all of which share the common feature of being a series of repeated trials that ultimately end in a \"winning\" trajectory. We also explore the ways in which microscopic parameters can be tuned to alter exploratory dynamics as well as the energetic burden of performing such processes. It is a great privilege to take part in this special volume dedicated to the life and work of Prof. Erich Sackmann (1934-2024). For one of us (R.P.), at the time of making a switch from traditional condensed matter physics to a life engaged in the study of life, he went to a meeting near Munich that completely opened his eyes to the ways in which the approach of physics could be brought to bear on the study of the living. Sackmann's work was an inspiring presence at that meeting. One of the hallmarks of his work was a principled approach to dissecting biological processes over a range of scales and phenomena. One common thread to much of his work was that it acknowledged the dynamical character of living organisms. The present paper attempts to follow in the tradition of Sackmann's studies of dynamics by suggesting a new way of looking at many biological processes all through the unifying perspective of what we will call exploratory dynamics.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tracing Erich Sackmann's Journey from Liquid Crystals to Biological Membranes.","authors":"Laurent Vonna,Laurent Limozin,Jacques Prost,Kheya Sengupta","doi":"10.1016/j.bpj.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.014","url":null,"abstract":"Biological membranes and liquid crystals are closely related because they exhibit similar types of molecular ordering and symmetry. This deep connection led many researchers in the '60s and '70s to cross back and forth between the two domains of research. Erich Sackmann crossed over early in his career, taking concepts and techniques from liquid crystal physics to membrane biology, and stayed to provide unique insights into the organisation and behaviour of membranes, helping to lay the foundations of physics of biological membranes and biophysics as we know it today. His mastery of liquid crystalline order, phase transition, anisotropy, and dynamics, naturally led him to fundamental properties of membrane-stacks, membranes and cytoskeletal mechanics. He helped establish simplified \"model membranes\" as a powerful tool to isolate and study specific aspects of membrane behaviour under controlled conditions and transfer this knowledge to biology.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"38 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Many will enter, few will win: Cost and sensitivity of exploratory dynamics.","authors":"Elena F Koslover, Milo M Lin, Rob Phillips","doi":"10.1016/j.bpj.2025.09.007","DOIUrl":"10.1016/j.bpj.2025.09.007","url":null,"abstract":"<p><p>A variety of biomolecular systems rely on exploratory dynamics to reach target locations or states within a cell. Without a mechanism to remotely sense and move directly toward a target, the system must sample over many paths, often including resetting transitions back to the origin. We investigate how exploratory dynamics can confer an important functional benefit: the ability to respond to small changes in parameters with large shifts in the steady-state behavior. However, such enhanced sensitivity comes at a cost: resetting cycles require energy dissipation to push the system out of its equilibrium steady state. We focus on minimalist models for two concrete examples: translational proofreading in the ribosome and microtubule length control via dynamic instability to illustrate the trade-offs between energetic cost and sensitivity. In the former, a driven hydrolysis step enhances the ability to distinguish between substrates and decoys with small binding energy differences. In the latter, resetting cycles enable catalytic control, with the steady-state length distribution modulated by substoichiometric concentrations of a reusable catalyst. Synthesizing past models of these well-studied systems, we show how path-counting and circuit-mapping approaches can be used to address fundamental questions such as the number of futile cycles inherent in translation and the steady-state length distribution of a dynamically unstable polymer. In both cases, a limited amount of thermodynamic driving is sufficient to yield a qualitative transition to a system with enhanced sensitivity, enabling accurate discrimination and catalytic control at a modest energetic cost.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yonggang Li,Satoshi Ii,Kazuyasu Sugiyama,Shigeho Noda,Vijay Rajagopal,Peter V S Lee,Xiaobo Gong
{"title":"A cross-scale analysis for the determinants of bonding dynamics on the distributions of rolling velocities of cells in microvessels.","authors":"Yonggang Li,Satoshi Ii,Kazuyasu Sugiyama,Shigeho Noda,Vijay Rajagopal,Peter V S Lee,Xiaobo Gong","doi":"10.1016/j.bpj.2025.09.011","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.011","url":null,"abstract":"The interplay between subcellular adhesion dynamics and cellular-scale deformations under shear flow drives key physiological and pathological processes. While both bond kinetics and fluid-cell interactions have been extensively studied in rolling adhesion, how bond characteristics quantitatively determine cellular velocity distributions remains unclear. In this study, we systematically investigate how force-free bond kinetics and intrinsic mechanical properties govern rolling adhesion dynamics, using macroscopic velocity distributions as a reference. By coupling the immersed boundary method with stochastic adhesion dynamics, we simulate rolling and deforming cells in straight microtubes with receptor-ligand interactions. Our results reveal that velocity distributions transition from log-normal to normal profiles when bond formation probabilities exceed a critical threshold, corresponding to bond saturation on the cell surface. Nonlinear effects of unstressed bond on/off rates on velocity distributions are observed, with distinct saturation thresholds for different bond types. Nonlinear bonds (modeled via the worm-like chain framework) exhibit fewer surface bonds at saturation compared to linear (Hookean) bonds. These cross-scale analyses of bond dynamics provide critical insights into interpreting cellular mechano-phenotypes through rolling behavior.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"86 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simon Wieland,Christina Steininger,David E Gitschier,Marius M Kaiser,Wolfgang Gross,Abdullah R Chaudhary,Jana Ritschar,Christian Laforsch,Adam G Hendricks,Holger Kress
{"title":"Main Manuscript for Many dynein teams collectively generate high forces during the transport of large organelles.","authors":"Simon Wieland,Christina Steininger,David E Gitschier,Marius M Kaiser,Wolfgang Gross,Abdullah R Chaudhary,Jana Ritschar,Christian Laforsch,Adam G Hendricks,Holger Kress","doi":"10.1016/j.bpj.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.012","url":null,"abstract":"The transport of organelles is important to maintain cellular organization and function. Efficient retrograde transport of large organelles with a size of several micrometers requires high collective forces from multiple dynein motors. However, the exact transport forces and their dependence on the cargo size are unknown for large organelles. Furthermore, it is not known how many dynein motors are active during this transport and how they to generate high collective forces sufficient to overcome the cytoplasmic drag. We measured forces generated during retrograde transport of phagosomes with diameters between 1 and 5 μm. Forces increased with phagosome volume and ranged from under 10 pN for the smallest up to 160 pN for the largest phagosomes. These forces matched the cytoplasmic drag to achieve equally fast transport with a velocity of 25 ± 4 nm s-1 for phagosomes of all sizes. To confirm the need for many dynein motors to generate such high forces, we labeled and quantified dynein on isolated phagosomes. We found up to 250 dyneins on the largest phagosomes and a dynein surface density which was independent of the phagosome size. We connected the dynein numbers and transport forces with a theoretical model of the microtubule distribution around the organelles. The model implies that because larger organelles displace and bend the microtubules, disproportionately large numbers of dyneins can be active and contribute to the high transport forces of large phagosomes. Our results indicate that during the transport of large organelles, many dyneins interact with multiple microtubules in a cargo size-dependent manner to achieve sufficiently large transport forces.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"35 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A transition of dynamic rheological responses of single cells: from fluid-like to solid-like.","authors":"Lin-Ru Qiao,Zhuo Chang,Chen-He Li,Jiu-Tao Hang,Xian-Jun Wu,Yu-Hang Xiao,Guang-Kui Xu","doi":"10.1016/j.bpj.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.010","url":null,"abstract":"The mechanical properties of cells are crucial for elucidating various physiological and pathological processes. Cells are found to exhibit a universal power-law rheological behavior at low frequencies. While they behave in a different manner at high frequency regimes, which leaves the transition region largely unexplored. Here, we investigate single-cell rheological behaviors across different cell types (primary hematopoietic stem cells, the hippocampal neuronal cell line and human dental pulp stem cells) by atomic force microscopy (AFM)-microrheology method, uncovering a universal two-stage power-law rheological behavior. Cells behave fluid-like at shorter time scales and solid-like at longer scales. To characterize the transition region between these stages, we introduce a time-scale parameter, termed \"transition time\". Notably, for all the cell types under study, we find that the transition time decreases with increasing elastic moduli and increases for larger power-law exponent. Furthermore, based on our previous self-similar hierarchical model, we propose a theoretical method to determine the upper and lower bounds of the transition time range. Our experimental results exhibit an excellent agreement, consistently falling within the predicted theoretical limits. Furthermore, we present six crucial mechanical indices that depict both the dynamic and static mechanical properties of single cells. These parameters can effectively differentiate cell types and provide a comprehensive perspective on the mechanical states of cells. Our study may offer new insights into the viscoelastic transformation of cells from fluid-like to solid-like behaviors, and highlights the mechanisms underlying various time scales during biomechanical processes.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"33 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clustering DNA and RNA molecular dynamics ensembles via secondary structure.","authors":"Swapnil Baral,Michael Zwolak","doi":"10.1016/j.bpj.2025.08.029","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.08.029","url":null,"abstract":"Macromolecular structure is central to biology. Yet, not all biomolecules have a well-defined fold. Intrinsically disordered regions are ubiquitous, conveying a versatility to function even in otherwise folded structures. For nucleic acids, entropic disorder is manifest in regions of incomplete base pairing (e.g., during transcription) and for long molecules (i.e., beyond the persistence length). To classify the resulting ensembles, we develop a method to cluster based on secondary structure, focusing specifically on DNA and RNA. The number of base pairs to reorganize furnishes a proper distance metric for structures of the same topology (e.g., without knots). This permits clustering of any type, from k-means to hierarchical to density-based methods. We demonstrate this by showing the broad distribution of secondary structure of a fragment of the M13 bacteriophage DNA and by revealing hidden order in a RNA Holliday junction. This clustering approach is connected to energy barriers from disrupting hybridization and recognizes structures that differ only by, e.g., internal reorientation as the same, compressing the vast free-energy landscape from entropic disorder.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"11 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zachary E Robinson,Higor Sette Pereira,Michael H D'Souza,Trushar R Patel
{"title":"Structural Dynamics of Dengue Virus UTRs and Their Cyclization.","authors":"Zachary E Robinson,Higor Sette Pereira,Michael H D'Souza,Trushar R Patel","doi":"10.1016/j.bpj.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.004","url":null,"abstract":"The dengue virus (DENV) poses a significant threat to human health, accounting for approximately 400 million infections each year. Its genome features a circular structure that facilitates replication through long-range RNA-RNA interactions, utilizing cyclization sequences located in the untranslated regions (UTRs). To gain new insights into the organization of the DENV genome, we purified the 5' and 3' UTRs of DENV in vitro and examined their structural and binding properties using various biophysical techniques combined with computational methods. Through our biophysical characterization, we determined the 5' and 3' UTR regions to bind with an affinity of 40 nM in a 1:1 stoichiometry. By using small-angle X-ray scattering (SAXS), we provide the first structural characterization of the 3' and 5' UTR regions, revealing several plausible conformations that the viral UTRs may adopt during replication. This comprehensive investigation revealed key features that provide mechanistic insights into the different structural states during DENV replication, as tracked through the accessibility of various RNA conformations. Overall, our research enhances the understanding of DENV cyclization, emphasising the structural adaptability, dynamic folding, and flexibility of these RNA molecules in solution. By uncovering details at the atomic level, we aim to contribute to the development of targeted drugs that can disrupt crucial stages of viral replication.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"16 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}