Biophysical journal最新文献

{"title":"Red Blood Cell Positional History, Sphericity, and Network Architecture Influence Lingering and Partitioning","authors":"Mohammed Bendaoud,Alexis Darras,Yazdan Rashidi,Christian Wagner,Chaouqi Misbah","doi":"10.1016/j.bpj.2026.09.024","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.024","url":null,"abstract":"The transport and distribution of red blood cells (RBCs) through microvascular networks is central to diverse applications in drug delivery, tissue engineering, and the study of pathological mechanisms. Recent findings highlight two critical phenomena: (i) a history-dependent partitioning effect, wherein the RBC partitioning at each bifurcation is influenced by the positional and configurational state inherited from previous bifurcations and (ii) RBC lingering at the bifurcation apex, which strongly affects downstream flow distribution. However, the interplay between network geometry, RBC sphericity (in spherocytosis disease), and these emergent behaviors remains insufficiently explored. Here, we perform two-dimensional Lattice Boltzmann simulations coupled with an immersed boundary model to systematically investigate RBC dynamics in both asymmetric and fully symmetric network designs. Our results show that RBC positional history grows progressively with each bifurcation, leading to increasing deviations from classical partitioning laws regardless of the network’s geometric complexity. We further demonstrate that even spherical RBCs can experience substantial lingering due to cumulative apex interactions, challenging the notion that only elongated or pathologically deformed cells are prone to these effects. These findings clarify how RBC deformability and prior apex encounters affect microcirculatory flow.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"32 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019694","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":"Truncating the Time-evolving Discrete Chemical Master Equation for Stochastic Biological Networks","authors":"Ali M. Farhat,Yiyu Pang,Farid Manuchehrfar,Ying Tang,Jie Liang","doi":"10.1016/j.bpj.2026.09.026","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.026","url":null,"abstract":"The discrete Chemical Master Equation (dCME) provides a rigorous framework for modeling stochastic biochemical reaction networks but suffers from an exponentially growing state space, making its direct solution intractable. Traditional truncation methods rely on trial-and-error approaches or finite state projections, often introducing inaccuracies by arbitrarily selecting state space boundaries. In this study, we present a truncation strategy for the exact solution of the time-evolving dCME. We provide a systematic and mathematically grounded framework to truncate the time-evolving dCME by leveraging transient solutions of independent birth-death processes. The theoretically estimated truncation bounds provide a conservative limit on computed errors, eliminating the need for heuristic state space selection. The framework also accounts for both upper and lower truncation boundaries, ensuring a conservative yet computationally efficient truncation strategy. These together enable the a priori determination of truncation points at each time step while maintaining a predefined probability error tolerance level. We apply this approach to diverse biochemical networks, including a single-gene expression model, an activation-inhibition feedback system, a genetic toggle switch, a feedforward genetic loop, and an enzymatic cascade network. The results demonstrate an efficient computation of time-evolving probability landscapes while preserving key stochastic properties such as multimodality. The present approach thus offers a significant advancement in solving the dCME by systematically balancing accuracy and computational efficiency. While previous truncation strategies were developed for the steady state, we introduce a theoretically grounded, time-dependent truncation framework that avoids relying on steady-state limits and instead computes probabilities only for states relevant at each time point.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"155 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019669","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":"Helium Nanodroplet Forcefield for Advancing Single-Molecule Serial Electron Diffraction Imaging","authors":"Eduardo R. Cruz-Chú,Andrew Clifford,Marisol Trejo,Yingbin Ge,Wei Kong,Peter Schwander","doi":"10.1016/j.bpj.2026.09.028","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.028","url":null,"abstract":"Single-molecule Serial Electron Diffraction (SS-EDI) is a promising methodology to determine biomolecular structures, which employs Helium Nanodroplets (HNDs) as the sample delivery system. Until now, structural determination methods have used liquid Helium only as a coolant, but SS-EDI offers a novel application for HNDs as an embedding matrix to isolate single molecules in an ultracold and weakly interacting fluid environment with minimal scattering. SS-EDI is still under active development and to advance it, researchers require an understanding of the interactions within HNDs at the nanoscale level. To support ongoing experimental efforts, we present a Molecular Dynamics (MD) forcefield for HNDs at 0.38 K, enabling direct calculation of electron diffraction patterns from atomic configurations. Our forcefield combines a Morse potential for van der Waals interactions with a Drude oscillator to capture polarization effects induced by charged dopants, and its parameters were validated against four key quantities of interest: bulk density, an upper bound for viscosity, droplet stability, and the radial profile of the average electron diffraction signal. During validation, we identified instabilities associated with polarizable model at ultralow temperatures, and mitigate them by reducing the effective polarizability, introducing an “ultracold” Drude particle, and employing canonical ensembles. Finally, we applied the forcefield to simulate HNDs doped with a tri-atom Argon ion, and the changes in electron diffraction profiles were compared with experimental measurements of HNDs of similar size. Despite significant statistical fluctuations in both simulation and experiment, the simulations reproduce the key peak positions observed experimentally, demonstrating qualitative agreement between them. These results establish MD simulations as a valuable tool to advance the application of liquid Helium as a new embedding matrix for structural determination.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"31 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013593","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 insights into ATP synthase c-ring accumulation in BMP-deficient lysosomes in Batten disease","authors":"Leonhard J. Starke,Erik K. Hansen,Kasparas Petkevicius,Anna L. Duncan","doi":"10.1016/j.bpj.2026.09.025","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.025","url":null,"abstract":"Bis(monoacylglycero)phosphate (BMP) is a signature lysosomal phospholipid that supports the catabolic functions of the lysosome. We recently demonstrated that BMP deficiency is associated with a variant of Batten disease, a neurodegenerative lysosomal storage disorder. This observation led us to investigate how BMP deficiency contributes to the previously reported accumulation of the ATP synthase c-ring in the lysosomes of Batten disease patients and preclinical models. The c-ring is an inner mitochondrial membrane (IMM) protein complex that interacts with cardiolipin, a mitochondrial phospholipid that shares structural features with BMP. Based on this, we hypothesised that BMP may perform an analogous function to cardiolipin in lysosomes. Specifically, we proposed that BMP preferentially interacts with the c-ring, dispersing it within lysosomal membranes and facilitating its degradation. To test this hypothesis, we conducted all-atom molecular dynamics simulations to examine the interactions of various BMP variants with the c-ring of human ATP synthase under different membrane conditions. We observed leaflet-specific preferential interactions of BMP with the protein interface. Replacement of BMP with anionic 16:0-18:1 phosphatidylglycerol (POPG) lipids resulted in a distinct binding mode and shorter residence time at the c-ring, indicating the importance of BMP’s unique structure with respect to protein binding. Furthermore, BMP enrichment was enhanced when using the physiologically relevant di-22:6 BMP variant in membranes containing polyunsaturated lipids and cholesterol. Overall, our study suggests that BMP promotes lysosomal c-ring degradation via c-ring co-localisation, whereas BMP deficiency in Batten disease drives c-ring accumulation.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"7 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010170","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":"Angle dependent forced separation and rolling calculations for VWF A1 variants bound to GPIbα","authors":"Yue Cheng,Zhipeng Xu","doi":"10.1016/j.bpj.2026.09.022","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.022","url":null,"abstract":"Binding between the von Willebrand factor (VWF) A1 domain and platelet glycoprotein Ibα (GPIbα) controls platelet capture under flow and changes when disease-associated A1 substitutions alter force-dependent bond lifetimes. We examined how disease-associated A1 substitutions affect bond mechanics under directional loading. Steered molecular dynamics (SMD) showed no significant effect of loading angle on peak separation force, whereas effective secant stiffness showed clear angle dependence. A1 remained structurally stable during pulling, while GPIbα underwent greater angle-dependent deformation and separation. Pooled rank comparisons between each variant and wild type (WT) identified R1334A as the case with lower peak separation force, consistent with disruption of the local R1334 interface, while R1306Q, R1450E, and G1324S showed largely overlapping SMD distributions with WT. For the R1306Q/R1450E rolling comparison, experimentally measured bond lifetimes were fitted with Bell slip kinetics to obtain force-dependent dissociation rates. Angle-dependent SMD mechanics were then used to relate tether extension to bond force, allowing the Bell slip kinetics to be coupled directly to a reduced ellipse rolling model with multiple load-bearing tethers. With increased load sharing, the R1450E/R1306Q velocity ratio reached 0.646, close to the experimental value of 0.607. A separate WT/G1324S calculation reproduced the shift in peak stopped-time stress from 16 to 32 dyn cm−2. Together, the model captured experimentally observed differences in both rolling dynamics and stopped-time behavior.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"81 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993799","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 Single-Particle Tracking Framework for Quantifying Intracellular Partition Free Energies","authors":"Malthe S. Nordentoft,Emilie Jessen,Enora Corsin,Judith Mine-Hattab,Mogens H. Jensen,Mathias S. Heltberg","doi":"10.1016/j.bpj.2026.09.023","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.023","url":null,"abstract":"Biomolecular condensates are membrane-less organelles that locally enrich specific molecules at spatial sites. A central challenge is determining the physical parameters of individual condensates, as their dimensions are typically below the diffraction limit of conventional microscopy. Single-particle tracking overcomes this limitation, but robust methods for extracting physical observables from trajectory collections remain scarce. Here, we present a framework for inferring the potential difference between molecules inside a condensate and those in the surrounding environment. We introduce a correction that accounts for condensate motion during acquisition, enabling reliable density estimation even from sparse data. After testing on in silico data, we apply our approach to 5 experimental datasets of proteins active in DNA repair and separate them based on the liquid nature of the focus.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"61 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993800","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":"Using endocytosis to switch between chemoattraction and chemorepulsion","authors":"Grace K. Luettgen,Brian A. Camley","doi":"10.1016/j.bpj.2026.09.021","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.021","url":null,"abstract":"White blood cells can be guided to targets by chemoattractant signals, but this response is complicated, including guidance toward and away from inflammation sites. We model how cells can switch between being attracted and repelled by a chemical signal. We study experiments on malignant B cell lines, which find that depending on their environment, B cells can either be attracted or repelled by signals like CCL19. The presence of chemorepulsion is also dependent on whether the receptors for CCL19 can be internalized via endocytosis. We develop a stochastic model of receptor-ligand binding and internalization where bound receptors drive a nonlinear feed-forward loop of intracellular signaling molecules, which determine the cell’s direction. We recapitulate key experimental results: changing CCL19 concentration or inhibiting receptor internalization can switch the cell’s direction. Our model implies that cells can navigate toward a target concentration of a signal, regulating that target by receptor internalization. We propose experiments to test this idea.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"13 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993824","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":"Rocking Without a Tune: Ex vivo and in vivo Responses to Sound in the Basilar Papilla of the Tokay Gecko","authors":"Brian L. Frost,Yuriria Vázquez,Kazuhiro Horii,Brian A. Fabella,A.J. Hudspeth","doi":"10.1016/j.bpj.2026.09.020","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.020","url":null,"abstract":"Like mammals, some reptiles possess sensitive and frequency-selective hearing at mid- to high-kilohertz frequencies. Both groups employ a place-frequency map within the inner ear to encode sound stimuli, but the mechanisms by which they achieve tuned nerve activation along the cochlea are believed to be distinct. To investigate the mechanical origins of auditory sensation in the reptiles, we measured sound-evoked displacement responses in the hearing organ of the tokay gecko (Gekko gecko), known as the basilar papilla. Using optical coherence tomography, we were able to resolve sub-nanometer-scale vibrations throughout the organ both in vivo and ex vivo. We saw that tuning was not present in the tissue-scale mechanics at any position within the organ; it instead exhibits an untuned rotational motion. We developed a mathematical model which predicted that this motion induces hair-bundle-stimulating fluid displacement, and is due to an anatomical asymmetry seen in many reptile species. These results are consistent with the theory that hair-bundle-level mechanics are primarily responsible for tuning in the tokay gecko cochlea, and we argue that our proposed mechanisms generalize to many other species across the Reptilia class.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"36 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148980623","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":"Zebrafish embryos are robust to local mechanical perturbations","authors":"Ming Hong Lui,Alejandro Jurado,Leon Lettermann,Timo Betz,Bart E. Vos","doi":"10.1016/j.bpj.2026.09.018","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.018","url":null,"abstract":"The investigation of morphogenesis during organism development has massively benefited from the interaction between developmental biology and biophysics, which gave new quantitative insights into nature’s physical working principles. The process of zebrafish epiboly provides a beautiful model system as cells exhibit collective migration, meanwhile requiring symmetry breaking for gastrulation and the subsequent tissue differentiation. These elegantly robust processes are facilitated by both biochemical and mechanical cues.\u0000Here we test the hypothesis that the future body axis is robust against local, non-lethal mechanical perturbations of tissue flow and tissue stress fields. For this, we trigger tissue flow by photoablation, which leads to an externally enforced symmetry breaking before natural symmetry breaking of gastrulation occurs. Using 3D light sheet microscopy, we obtained nuclei trajectories as a proxy for the migration of individual cells. Analyzing the derived tissue velocity field, we observed that epiboly is highly robust and mostly unaffected by ablation damage. However, the photoablation induced a convergent motion of cells towards an azimuthal angle resembling shield formation. We extensively characterized this convergent motion and checked if this tissue flow is able to reorient natural symmetry breaking during shield formation. While ablations can transiently disrupt or reorient the convergent motion, we cannot confirm any redirection of the location where the future body axis of the animal develops. The observations were also highly dependent on the developmental stage of the embryo, which cast a greater and more permanent impact, suggesting strong control exerted by factors other than mechanical signals.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"396 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148980621","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":"Interactions between single actin and vimentin filaments","authors":"Pallavi Kumari,Sascha Lambert,Komal Bhattacharyya,Kristian A.T. Pajanonot,Stefan Klumpp,Sarah Köster","doi":"10.1016/j.bpj.2026.09.017","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.017","url":null,"abstract":"The cytoskeleton determines cell shape, mechanical properties, and motility by interconnected networks of protein filaments – actin filaments, microtubules and intermediate filaments. Their collective function relies on crosstalk between these filament systems, yet the physical basis of interactions between the filaments remains insufficiently understood. Actin and vimentin filaments and networks frequently co-localize within cells and jointly regulate contractility, force transmission and mechanical resilience, indicating functional cooperation. However, it remains unclear whether these interactions arise from direct filament–filament interactions or are mediated exclusively by accessory crosslinking proteins. Studies of reconstituted composite networks probing direct interactions by rheology have yielded differing results. Here, we show that single actin filaments and vimentin intermediate filaments do indeed interact directly, forming force-bearing contacts in the absence of crosslinking proteins, with interaction strengths comparable to other previously reported cytoskeletal filament pairs. Using quadruple optical tweezers combined with microfluidics and confocal microscopy, we systematically probe these interactions under controlled conditions across a range of ionic environments. We find that, in contrast to other filament pairs, variations in ionic strength do not appreciably affect the interaction breaking forces between actin and vimentin filaments. However, the interaction geometry determines the achievable interaction strengths, because the limited stretchability of the actin filaments sets an upper bound to the measurable force range. This limit also imposes a restriction on direct quantification of interaction parameters, which we circumvent by a Bayesian unmasking strategy that allows us to infer bond parameters despite the breaking of actin filaments. These findings demonstrate that actin and vimentin form a mechanically interacting system through direct filament bonds, and our work quantifies the interaction forces between the two filament types in the absence of crosslinking proteins.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"38 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148980648","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}