Biophysical journal最新文献

{"title":"Time-dependent active force drives periodic reversal in collective cell migration.","authors":"Chen-He Li,Xu Yin,Shuang-Quan He,Guang-Kui Xu","doi":"10.1016/j.bpj.2025.08.011","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.08.011","url":null,"abstract":"Collective cell migration is prevalent in the processes of embryo development, wound healing, and cancer metastasis across various space and time scales. While various motion modes have been identified, their relationships with single cell motility and the underlying mechanisms remain poorly understood. In this study, we develop an active vertex model to investigate the spatiotemporal behavior of collective cells confined in annulus domain, accounting for the polarity memory effect of individual cells and the impact of confinement size. We reveal that cells spontaneously undergo periodic reversals in the rotation direction, with the inner boundary acting as the origin of initiation. The polarity delay with velocity and the growth of passive forces contribute to the reversals. The reversal frequency increases with the memory decay rate while remaining largely insensitive to the activity strength. In addition, we propose a polar order parameter to characterize various motion modes across a wide range of parameter spaces. This parameter effectively identifies four distinct dynamic regimes: global rotation (GR), periodic reversal (REV), oscillation (OSC), and local swirling (LS). Our findings establish a framework for understanding the persistence of collective cell migration under geometric confinements and underscore the timescale required for molecular rearrangements during polarization.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"9 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851148","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 ionic electrodiffusion and ephaptic coupling in cardiac dynamics.","authors":"Ning Wei,Yoichiro Mori","doi":"10.1016/j.bpj.2025.08.008","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.08.008","url":null,"abstract":"Cardiac myocytes coordinate the heart contractions through electrical signaling, facilitated by gap junctions (GJs) in the intercalated disc (ID). GJs provide low-resistance pathways for electrical propagation between myocytes, acting as the main mechanism for electrical communication in the heart. However, studies show that conduction can persist in the absence of GJs. For instance, GJ knockout mice still display slow and discontinuous electrical propagation, suggesting the presence of alternative communication mechanisms. Ephaptic coupling (EpC) serves as an alternative way for cell communication, relying on electrical fields within narrow clefts between neighboring myocytes. Studies show that EpC can enhance conduction velocity (CV) and reduce conduction block (CB), especially when GJs are compromised. Reduced GJs and significant electrochemical gradients are prevalent in various heart diseases. However, existing models often fail to capture their combined influence on cardiac conduction, which limits our understanding of both the physiological and pathological aspects of the heart. Our study aims to address this gap through the development of a two-dimensional (2D) discrete multidomain electrodiffusion model that includes EpC. In particular, we investigated the interplay between EpC and multidomain electrodiffusion on action potential (AP) propagation, morphology, and electrochemical properties. Our findings indicate that under strong EpC, Na + electrodiffusion enhances CV, reduces the occurrence of CB, and sharpens the upstroke phase of the AP, while Ca 2+ and K + diffusion shorten the AP duration, alter the repolarization phase, and elevate the resting membrane potential. Additionally, when EpC is prominent, Na + electrodiffusion helps stabilize AP propagation and promotes its spread into ischemic regions. Strong EpC also significantly alters ionic concentrations in the cleft, markedly increasing [K +], nearly depleting [Ca 2+], and causing moderate changes in [Na +]. This multidomain electrodiffusion model provides valuable insights into the mechanisms of EpC in the heart.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"37 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825257","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":"Quantifying the potential of Thermal Highways to facilitate Long Range Proton Transport in Enzymes.","authors":"Yann Chalopin,Louis Milhamont,Malcolm Buckle","doi":"10.1016/j.bpj.2025.07.044","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.07.044","url":null,"abstract":"Proton transport in enzymes is often portrayed as a purely static, hydrogen-bond-mediated relay, yet this view neglects how ultrafast vibrational coherence within the protein fold can mechanically drive long-range transfer. Here, we introduce the vibrational-entropy flux tensor to identify thermal highways-evolutionarily conserved networks of residues whose synchronized terahertz-frequency phonons transiently compress donor-acceptor distances. Using parameter-free coarse-grained elastic-network models of [FeFe]-hydrogenase, we show that these highways boost quantum-tunneling probabilities by 10-100× (depending on mode frequency), directly linking picosecond-scale dynamics to increased proton flux. A single-value descriptor, Tlim, defined as the minimum entropy-flux along a proton wire, explains 90% of the variance in H 2-production rates across ten enzyme variants (R=0.90). Crucially, mutations >10 Å from the active site that disrupt thermal-highway connectivity proportionally attenuate both Tlim and catalytic turnover-evidence that long-range, fold-encoded phonon coherence is a mechanistic driver of proton transport. Our multiscale framework unifies static chemical models with dynamic phonon-mediated enhancement, offering a predictive route for engineering proton-coupled catalysts in bioenergy and beyond.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"1 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805739","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.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.08.004","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811676","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":"Multi-scale simulations of MUT-16 scaffold protein phase separation and client recognition.","authors":"Kumar Gaurav, Virginia Busetto, Diego Javier Páez-Moscoso, Arya Changiarath, Sonya M Hanson, Sebastian Falk, René F Ketting, Lukas S Stelzl","doi":"10.1016/j.bpj.2025.08.001","DOIUrl":"10.1016/j.bpj.2025.08.001","url":null,"abstract":"<p><p>Phase separation of proteins plays a critical role in cellular organization. How phase-separated protein condensates underpin biological function and how condensates achieve specificity remain elusive. We investigated the phase separation of MUT-16, a scaffold protein in Mutator foci, and its role in recruiting the client protein MUT-8, a key component in RNA silencing in Caenorhabditis elegans. We employed a multi-scale approach that combined coarse-grained (residue-level CALVADOS2 and near-atomistic Martini3) and atomistic simulations. Simulations across different resolutions provide a consistent perspective on how MUT-16 condensates recruit MUT-8, enabling the fine-tuning of chemical details and balancing the computational cost. Both coarse-grained models (CALVADOS2 and Martini3) predicted the relative phase-separation propensities of MUT-16's disordered regions, which we confirmed through in vitro experiments. Simulations also identified key sequence features and residues driving phase separation and revealed differences in residue interaction propensities between CALVADOS2 and Martini3. Furthermore, Martini3 and 350-μs atomistic simulations on Folding@Home of MUT-8's N-terminal prion-like domain with MUT-16 M8BR cluster highlighted the importance of cation-π interactions between Tyr residues of MUT-8 and Arg residues of MUT-16 M8BR. Lys residues were observed to be more prone to interact in Martini3. Atomistic simulations revealed that the guanidinium group of Arg also engages in sp²-π interactions and hydrogen bonds with the backbone of Tyr, possibly contributing to the greater strength of Arg-Tyr interactions compared to Lys-Tyr, where these additional favorable contacts are absent. In agreement with our simulations, in vitro co-expression pull-down experiments demonstrated a progressive loss of MUT-8 recruitment after the mutation of Arg in MUT-16 M8BR to Lys or Ala, confirming the critical role of Arg in this interaction. These findings advance our understanding of MUT-16 phase separation and subsequent MUT-8 recruitment, key processes in assembling Mutator foci that drive RNA silencing in C. elegans.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803367","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":"Cooperativity in septin polymerization is tunable by ionic strength and membrane adsorption.","authors":"Ellysa J D Vogt, Ian Seim, Wilton T Snead, Brandy N Curtis, Amy S Gladfelter","doi":"10.1016/j.bpj.2025.08.005","DOIUrl":"10.1016/j.bpj.2025.08.005","url":null,"abstract":"<p><p>Cells employ cytoskeletal polymers to move, divide, and pass information inside and outside of the cell. Previous work on eukaryotic cytoskeletal elements such as actin, microtubules, and intermediate filaments investigating the mechanisms of polymerization have been critical to understand how cells control the assembly of the cytoskeleton. Most biophysical analyses have considered cooperative versus isodesmic modes of polymerization; this framework is useful for specifying functions of regulatory proteins that control nucleation and understanding how cells regulate elongation in time and space. The septins are considered a fourth component of the eukaryotic cytoskeleton, but they are poorly understood in many ways despite their conserved roles in membrane dynamics, cytokinesis, and cell shape, and in their links to a myriad of human diseases. Because septin function is intimately linked to their assembled state, we set out to investigate the mechanisms by which septin polymers elongate under different conditions. We used simulations, in vitro reconstitution of purified septin complexes, and quantitative microscopy to directly interrogate septin polymerization behaviors in solution and on synthetic lipid bilayers of different geometries. We first used reactive Brownian dynamics simulations to determine if the presence of a membrane induces cooperativity to septin polymerization. We then used fluorescence correlation spectroscopy to assess septins' ability to form filaments in solution at different salt conditions. Finally, we investigated septin membrane adsorption and polymerization on planar and curved supported lipid bilayers. Septins clearly show signs of salt-dependent cooperative assembly in solution, but cooperativity is limited by binding a membrane. Thus, septin assembly is dramatically influenced by extrinsic conditions and substrate properties and can show properties of both isodesmic and cooperative polymers. This versatility in assembly modes may explain the extensive array of assembly types, functions, and subcellular locations in which septins act.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803366","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":"Molecular Dynamics Simulations Reveal Subtle Consequences of H3 K9 and K27 Tri-Methylation.","authors":"Stephanie Portillo-Ledesma,Zilong Li,Tamar Schlick","doi":"10.1016/j.bpj.2025.08.002","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.08.002","url":null,"abstract":"Epigenetic modifications of histone tails are key mechanisms of genome regulation. In particular, tri-methylation of Lysines (K) 9 and 27 of the histone H3 tail are important for genome silencing. In this work, we explore by all-atom molecular dynamics simulations the effect of these two epigenetic marks on the structure and interactions of the H3 tail in several contexts: isolated tails, nucleosomes, chromatosomes, and stacked nucleosomes. Overall, we find that although the isolated tails do not show significant conformational changes upon methylation, a more flexible and extended H3 tail compared to the native tail results in the nucleosome systems, with K9 methylation effects more profound. This change could facilitate the interaction of the tail with protein readers like HP1 or PcG. We also observe that both methylations increase the interactions of the H3 tail with the linker DNA in the context of the chromatosome, producing a chromatosome with tighter linker DNA, which could favor chromatin compaction. For stacked nucleosomes mimicking i±2 zigzag interactions, we see that methylation of either K9 or K27 reduces the interactions of one of the H3 tails with its parental nucleosome and increases its interactions with the non-parental nucleosome, which could also help compact the chromatin fiber. In the three nucleosome-containing systems, we observe an asymmetry between the two tails, especially in the chromatosome, where one tail extends to interact with the linker DNA. This asymmetry modulates the effect that methylation has on each tail. Thus, overall, methylations of K9 and K27 have a subtle but notable impact on the H3 tail structure and its interactions within the chromatin fiber. These results help explain how this epigenetic modification compacts chromatin fibers and promotes longer-range interactions; these changes also guide how to approximate these effects in coarse-grained chromatin models.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"16 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796963","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":"The role of hydrophobic collapse in cytotoxic and functional amyloid oligomerization.","authors":"Kelsie M King,Hajar Zaheer,Anne M Brown","doi":"10.1016/j.bpj.2025.07.042","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.07.042","url":null,"abstract":"Amyloid refers to an insoluble, highly organized protein fibril composed of intermolecular β-sheets, known as a cross-β motif. Amyloidogenic proteins are generally driven to aggregate into tightly packed fibrils. Some amyloids are functional, often being utilized as hormone storage reservoirs. The functional, paracrine signaling neuropeptide β-endorphin (βE) is stored and released to modulate pain responses. Conversely, the function of amyloid-β (Aβ), involved in Alzheimer's disease, is uncertain - but substantial evidence exists of its role in neuronal cell apoptosis. While both peptides are mechanistically linked in their propensity to adopt fibrillar structures, the biophysical characteristics that drive divergence in cytotoxic potential are not well understood. To probe the conformational dynamics and mechanisms of functional and cytotoxic oligomer formation, we utilized all-atom molecular dynamics (MD) to simulate the formation of monomeric and hexameric Aβ42 and βE31. Monomeric Aβ42 and βE31 selectively sampled β-strand motifs comprised of hydrophobic residues, adopting a collapsed state. Cluster analysis indicates that βE31 hexamers were more conformationally diverse than those sampled by Aβ42, suggesting βE31 exhibits more signatures of disorder. Aβ42 hexamer formation was driven by hydrophobic packing of collapsed β-strand motifs, where βE31 hexamer peptide subunits remained structurally plastic and solvent accessible. Mutation of Aβ42 disrupting the C-terminal hydrophobic sequence inhibited hydrophobic β-strand formation, reduced aggregation propensity and increased solvent accessibility, suggesting retention of a collapsed state is critical for aberrant oligomer formation. This work provides a preliminary view of cytotoxic and functional oligomer morphologies at atomistic resolution, gaining insights into the biophysical aspects of early aggregation events of amyloids.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796917","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":"Revealing the glutamate switch: insights into proton translocation in plant H+-pyrophosphatase.","authors":"Yu-Sung Huang,Jia-Yin Tsai,Shih-Ming Lin,Sheng-Chia Wang,Chwan-Deng Hsiao,Yuh-Ju Sun","doi":"10.1016/j.bpj.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.08.003","url":null,"abstract":"Membrane-bound pyrophosphatases (M-PPases) are responsible for the hydrolysis of pyrophosphate (PPi), coupled with the pumping of H+ and/or Na+ across the membrane. In Vigna radiata H+-translocating pyrophosphatase (VrH+-PPase), proton translocation involves both a \"binding change\" mechanism, where PPi binding induces proton translocation, and the \"Grotthuss-chain\" mechanism, which describes proton translocation along the ion gate, hydrophobic gate, and exit channel. However, the dynamic coupling between protonation states and conformational changes in VrH+-PPase remains unclear, partly due to the challenges of experimentally capturing transient states during transport. To address this, we employed constant pH molecular dynamics (CpHMD) and classical molecular dynamics (MD) simulations to elucidate the proton transport mechanism from the ion gate (R242/D294/K742/E301) to the hydrophobic gate (L232/A305/L555/V746). Our simulations reveal that K742 becomes deprotonated upon PPi binding, suggesting its potential role as an internal proton donor. When K742 is deprotonated, E301 penetrates the hydrophobic gate and creates a hydrophilic environment for proton transport. Following PPi hydrolysis, D294 accepts a hydrolysis-generated proton to become protonated, inducing R242 to act as a positive plug that prevents the re-protonation of D294. Meanwhile, the protonation of D294 causes E301 to rebound and close the hydrophobic gate. We propose that E301 acts as a molecular switch, regulating proton transport through the hydrophobic gate. Furthermore, we suggest the penetration of glutamate is a conserved feature among plant H+-PPases, maintaining a consistent hydrophilic environment at the hydrophobic gate in H+-PPases. In conclusion, proton translocation in plant H+-PPases involves lysine deprotonation in the PPi-bound state and aspartate protonation in the PPi-hydrolyzed states, with glutamate switch dynamically regulating the opening and closing of the hydrophobic gate.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"6 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792092","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":"Effectiveness of outer hair cells as cochlear amplifier: In simple model systems.","authors":"Kuni H Iwasa","doi":"10.1016/j.bpj.2025.05.029","DOIUrl":"10.1016/j.bpj.2025.05.029","url":null,"abstract":"<p><p>Cochlear outer hair cells (OHCs) have two mechanosensitive elements: the hair bundle (HB) with mechanotrasducer channels and the piezoelectric lateral wall of the cell body. The present report examines how these elements interact with each other by incorporating OHCs into the simplest local cochlear models. In the frequency range, typically above 1 kHz, where capacitive conductance is greater than the ionic conductance, HB conductance drives the piezoelectric cell body and amplified oscillation by countering viscous drag, whereas the cell body increases its stiffness owing to strain-induced polarization, elevating the resonance frequency. Since HB sensitivity is essential for amplification, the resonance is not pure piezoelectric but semi-piezoelectric. In the lower-frequency range, typically lower than 100 Hz, strain-induced polarization contributes to drag, and the HB sensitivity increases cell body stiffness.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2383-2390"},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233068","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}