Biophysical journalPub Date : 2025-06-17Epub Date: 2025-05-05DOI: 10.1016/j.bpj.2025.04.033
Rui Jiang, Qingzhou Feng, Daguan Nong, You Jung Kang, David Sept, William O Hancock
{"title":"Motor clustering enhances kinesin-driven vesicle transport.","authors":"Rui Jiang, Qingzhou Feng, Daguan Nong, You Jung Kang, David Sept, William O Hancock","doi":"10.1016/j.bpj.2025.04.033","DOIUrl":"10.1016/j.bpj.2025.04.033","url":null,"abstract":"<p><p>Intracellular vesicles are typically transported by a small number of kinesin and dynein motors. However, the slow microtubule binding rate of kinesin-1 observed in in vitro biophysical studies suggests that long-range transport may require a high number of motors. To address the discrepancy in motor requirements between in vivo and in vitro studies, we reconstituted motility of 120-nm-diameter liposomes driven by multiple GFP-labeled kinesin-1 motors. Consistent with predictions based on previous binding rate measurements, we found that long-distance transport requires a high number of kinesin-1 motors. We hypothesized that this discrepancy from in vivo observations may arise from differences in motor organization and tested whether motor clustering can enhance transport efficiency using a DNA scaffold. Clustering just three motors increased liposome travel distances across a wide range of motor numbers. Our findings demonstrate that, independent of motor number, the arrangement of motors on a vesicle regulates transport distance, suggesting that differences in motor organization may explain the disparity between in vivo and in vitro motor requirements for long-range transport.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2033-2040"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysical journalPub Date : 2025-06-17Epub Date: 2025-05-05DOI: 10.1016/j.bpj.2025.04.025
Ram M Adar
{"title":"Separation of ionic timescales explains dynamics of cellular volume regulation.","authors":"Ram M Adar","doi":"10.1016/j.bpj.2025.04.025","DOIUrl":"10.1016/j.bpj.2025.04.025","url":null,"abstract":"<p><p>Living cells actively regulate their volume in response to changes in the extracellular environment, such as osmolarity and chemoattractant concentration. While the basic physical mechanisms of volume regulation are understood from the classic \"pump-leak\" model, it does not provide an explicit expression for the volume during dynamic regulation and can benefit from further insight into the volume dynamics. Here, we propose a simple explanation of volume dynamics in terms of two phases: fast volume adjustment to membrane potential, largely determined by Cl<sup>-</sup> leakage, and slow potential adaptation after shock, constrained by Na<sup>+</sup> leakage. The volume change may predominantly occur in either of these two phases, as we demonstrate for the scenarios of regulatory volume decrease and increase. Our theoretical predictions are validated by two recent independent shock experiments: osmotic shocks in HeLa cells and neutrophil activation upon sudden exposure to chemoattractants. Our theory aims to elucidate cellular volume dynamics on the scale of tens of minutes in various biological contexts.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1944-1951"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation and refinement of all-atom force fields for reproducing collagen structure and dynamics.","authors":"George A Pantelopulos,Robert B Best","doi":"10.1016/j.bpj.2025.06.013","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.013","url":null,"abstract":"Collageneous protein domains, characterized by the XYGly sequence repeat motif, trimerize and fibrilize to serve as the molecular skeleton of extracellular matrices and their mutations are frequently associated with disease. Because of experimental challenges in studying the effect of mutations on the properties of collagen, accurate atomistic Molecular Dynamics (MD) simulations are an invaluable tool. We evaluate the accuracy of state of the art MD force fields using recent experiments on model peptide homotrimers composed of Proline-4(R)-Hydroxyproline-Glycine (POG) repeats: the stabilizing POG motif appears with high frequency in several types of collagen. POG-repeats are used as templates to explore the role of amino acid substitutions in modulating collagen structure. We have compared the structure and dynamics of collagen POG10 homotrimers with various force fields from the CHARMM, AMBER, and GROMOS families together with various water models to aggregated crystal structure data, NMR data, and SAXS form factors. Of the tested force fields, we find those from AMBER and CHARMM give an acceptable description of collagen structure. AMBER force fields accurately reproduce collagen dihedrals, side chain torsions, amide spin relaxations, and SAXS data. CHARMM force fields were found to systematically shift backbone ϕ and ψ dihedrals, adopt incorrect side chain torsional angles, and overstructure POG10, increasing the persistence length relative to POG10 in AMBER force fields. However, by scaling the CHARMM36 CMAP terms of all dihedrals in POG10, we are able to capture a level of accuracy relative to experiment similar to that for the AMBER force fields. We suggest the use of AMBER ff99sb force fields or CHARMM36 with CMAP terms involving Pro, Hyp, and Gly rescaled by a factor of 1/2 (which we term CHARMM36mGP) for modeling collagen-like peptides.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"5 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320101","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}
Biophysical journalPub Date : 2025-06-17Epub Date: 2025-05-02DOI: 10.1016/j.bpj.2025.04.030
Xiangdong Kong, Zheng Zhong, Chao Fang
{"title":"F-actin dynamics regulates collective cell migration by modulating cell shape and stress correlation.","authors":"Xiangdong Kong, Zheng Zhong, Chao Fang","doi":"10.1016/j.bpj.2025.04.030","DOIUrl":"10.1016/j.bpj.2025.04.030","url":null,"abstract":"<p><p>As an essential component in generating cell contractility, F-actin plays a pivotal role in collective cell migration. However, the mechanisms by which subcellular F-actin dynamics influence the collective behaviors of cell clusters across scales remain poorly understood. In this study, we developed a mechanical model to investigate how the dynamics of stress fibers and cryptic lamellipodia, prominent F-actin structures generating traction forces, regulate collective cell migration. Our results show that strengthening stress fibers significantly amplifies cell rearrangements and counteracts the high-density-induced inhibition of cell movements in the monolayer. It is attributed to the tension-caused cell elongation, which facilitates the growth of normalized mean-squared displacements in high-density cell monolayers. Moreover, the model shows that stronger stress fibers could effectively guide collaborative cell movements through enhancing the spatial correlation of maximum principal stress. Additionally, we found cryptic lamellipodia exhibit similar influence on collective cell migration. Our results bridge intracellular F-actin dynamics with collective cell migration, offering insights into the underlying mechanisms and their biological significance.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1995-2004"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuan Fang,Peter Varughese,Sara Osorio-Valencia,Aleksey V Zima,Peter M Kekenes-Huskey
{"title":"A Bayesian framework for systems model refinement and selection of calcium signaling.","authors":"Xuan Fang,Peter Varughese,Sara Osorio-Valencia,Aleksey V Zima,Peter M Kekenes-Huskey","doi":"10.1016/j.bpj.2025.06.010","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.010","url":null,"abstract":"Calcium (Ca2+) is a crucial messenger that modulates contractile and electrophysiological processes in eukaryotic cells. Dysregulation of Ca2+-signaling influences these processes and is strongly associated with diseases such as cancer, immune disorders, and heart failure. Computational modeling of Ca2+ dynamics offers valuable insights into these processes. However, traditional approaches often overlook the inherent heterogeneity within cell populations, including cell-to-cell variability and population-wide differences. To overcome these limitations, we developed and implemented an advanced statistical approach (a Bayesian inference framework using a hierarchical mixture architecture) specifically engineered to capture and model the diverse behaviors seen in fundamental calcium signaling pathways within cells. We applied this framework to myoblasts and to a HEK293 cell line expressing the cardiac proteins SERCA2a and RyR2. Using fluorescence microscopy, we monitored Ca2+ dynamics in response to extracellular adenosine triphosphate (ATP), as well as spontaneous Ca2+ release and uptake between cellular compartments. Our framework leverages the microscopy data to identify the most probable models and parameters that reproduce experimental observations, effectively distinguishing multiple clusters of cells with distinct kinetic behaviors. This approach provides deeper insights into the underlying biological processes and their variability across multiple populations of cells. Our findings demonstrate that this Bayesian method significantly improves our ability to create accurate computational models of Ca2+ signaling by explicitly accounting for cellular differences. This, in turn, enhances our capacity to understand the complex regulatory networks that govern how cells use calcium signals.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"15 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311477","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":"Estimating physical conditions supporting gradients of ATP concentration in the eukaryotic cell.","authors":"Rajneesh Kumar, Iain G Johnston","doi":"10.1016/j.bpj.2025.06.016","DOIUrl":"10.1016/j.bpj.2025.06.016","url":null,"abstract":"<p><p>The ATP molecule serves as an energy currency in eukaryotes (and all life), providing the energy needed for many essential cellular processes. But the extent to which substantial spatial differences exist in ATP concentration in the cell remains incompletely known. It is variously argued that ATP diffuses too quickly for large gradients to be established, or that the high rates of ATP production and use (sources and sinks) can support large gradients even with rapid diffusion-and microscopic models and detailed experiments in different specific cases support both pictures. Here, we attempt a mesoscopic investigation, using reaction-diffusion modeling in a simple biophysical picture of the cell to attempt to ask, generally, which conditions cause substantial ATP gradients to emerge within eukaryotic cells. If ATP sources (like mitochondria) or sinks (like the nucleus) are spatially clustered, large fold changes in concentration can exist across the cell; if sources and sinks are more spread, then rapid diffusion indeed prevents large gradients from being established. This dependence holds in model cells of different sizes, suggesting its generality across cell types. Our theoretical work will complement developing intracellular approaches exploring ATP concentration inside eukaryotic cells.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315813","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 Contemporary View of Mechanosensory Transduction in Auditory Hair Cells.","authors":"Matthew Mun,Jeffrey R Holt","doi":"10.1016/j.bpj.2025.06.015","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.015","url":null,"abstract":"The ability to transduce the mechanical stimuli that initiate vertebrate hearing and balance is enabled by the stereociliary tips of inner ear hair cells, where a complex protein machine serves as a nexus for mechanosensory transduction (MT). The culmination of over two decades of work has illuminated many essential components of this protein complex, including the identification of TMC1 and TMC2, TMIE and CIB2 as obligatory subunits of hair cell MT channels. In this review, we highlight the work and history that has informed contemporary understanding of mechanosensory transduction, recent advances and challenges in characterizing MT proteins both individually and in context of the greater complex, and future directions necessary to fully understand the nature of hair cell MT and its molecular mechanisms.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"12 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311478","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}
Mara Smite, Mihails Birjukovs, Peteris Zvejnieks, Ivars Drikis, Guntars Kitenbergs, Andrejs Cebers
{"title":"Explicit analysis of magnetotactic bacteria motion reveals the length scaling of magnetic moments","authors":"Mara Smite, Mihails Birjukovs, Peteris Zvejnieks, Ivars Drikis, Guntars Kitenbergs, Andrejs Cebers","doi":"10.1016/j.bpj.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.008","url":null,"abstract":"Magnetotactic bacteria (MTB) are a diverse group of microorganisms whose movement can be directed via a magnetic field, which makes them attractive for applications in medicine and microfluidics. One of their key properties is the magnetic moment <ce:italic>m</ce:italic>, which is challenging to measure. We perform optical imaging experiments with MSR-1 MTB, and derive both the <ce:italic>m</ce:italic> statistics and the scaling of <ce:italic>m</ce:italic> with the MTB size using an explicit and fully automated method to determine <ce:italic>m</ce:italic> from the MTB trajectories via the U-turn protocol, which measures <ce:italic>m</ce:italic> based on the U-shaped trajectories exhibited by the MTB in an applied alternating magnetic field. The proposed method is an alternative to the standard U-turn time-based moment calculation and uses the theoretical U-turn shape function we have derived. This directly accounts for the U-turn geometry and determines the moment from the U-turn branch width. We couple this approach with a robust U-turn decomposition algorithm that detects U-turns from MTB tracks regardless of their orientations. We report a linear dependence of <ce:italic>m</ce:italic> on the size of the bacteria, accounting for the bacteria velocity variations during the U-turns. We also show that the new U-turn shape-based and the conventional time-based methods produce significantly different results. The proposed method can be used to differentiate between various types of MTB within the same population based on their velocity and magnetic moments, and to precisely characterize the magnetic properties of a culture.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"5 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289817","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":"Ultrasonic detection of α-synuclein amyloid seeds from a highly crowded environment.","authors":"Tomoki Ota, Kichitaro Nakajima, Keiichi Yamaguchi, Yuji Goto, Hirotsugu Ogi","doi":"10.1016/j.bpj.2025.06.006","DOIUrl":"10.1016/j.bpj.2025.06.006","url":null,"abstract":"<p><p>Detecting α-synuclein (α-Syn) amyloid seeds in biological fluids is a promising approach for the early diagnosis of Parkinson's disease. However, detecting subtle amounts of seeds in highly crowded environments remains challenging. Ultrasonication can enhance seed detection by efficiently fragmenting fibrils, but its effects in crowded environments have not been fully explored. In this study, we apply ultrasonication to detect α-Syn seeds in a highly crowded milieu and investigate its effects on seed detection. Our results show that ultrasonication enables rapid detection of α-Syn seeds with a detection limit of 10 pg/mL, even in the presence of 40 mg/mL serum albumin. Intriguingly, the amount of fibril formed depends on the initial seed concentration in a crowded environment only under ultrasonication. To understand this phenomenon, we theoretically analyze the kinetics of seed-dependent amyloid formation. The results suggest that ultrasonic cavitation induces the formation of a dead-end complex between serum albumin and α-Syn monomers, which can reduce false positives by suppressing seed-independent amyloid formation. These findings demonstrate ultrasonication as a powerful tool for the sensitive detection of α-Syn seed in clinical diagnostics.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274061","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":"Propofol Inhibits Piezo Mechanosensitive Channels.","authors":"Donggyeom Yu, Chilman Bae","doi":"10.1016/j.bpj.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.005","url":null,"abstract":"<p><p>Modulation of ion channels is a key mechanism by which anesthetics exert their effects. Propofol, a widely used anesthetic, has been shown to influence mechanosensitive ion channels (MSCs), though the details of this interaction remain under investigation. In this study, we show that propofol inhibits Piezo mechanosensitive channels using electrophysiological recordings and calcium imaging in HEK293T cells overexpressing human Piezo1 (hP1) and Piezo2 (hP2) channels. At 50 μM, propofol inhibited hP1 currents across multiple configurations (outside-out, whole-cell, and cell-attached) with a dissociation constant of 51.6 ± 24.0 μM. The stimulus-response curve shifted to the right, with an increase in the half-maximal pressure by 14 mmHg. Propofol selectively inhibited hP1 gating by stabilizing the closed state without affecting channel conductance or slope sensitivity. It also significantly reduced Yoda1-induced calcium influx in hP1-overexpressing cells. In hP2 channels, propofol inhibited whole-cell currents by reducing channel open probability while leaving conductance unchanged. Conversely, 1 mM isoflurane did not affect hP1 or hP2 currents in the outside-out configuration. These findings suggest a possible contribution of inhibition of mechanosensitive Piezo channels, providing new insights into its mechanism of action.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246245","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}