Biophysical journal最新文献_第6页

Neurofilament transport kinetics can be explained by the activity of small numbers of independent kinesin and dynein motors 神经丝运输动力学可以用少量独立的动力蛋白和动力蛋白马达的活动来解释

IF 3.4 3区生物学

Biophysical journal Pub Date : 2026-09-16 DOI: 10.1016/j.bpj.2026.09.016

Rawan M. Nowier,Christopher M. Johnson,J. Daniel Fenn,Anthony Brown,Peter Jung

{"title":"Neurofilament transport kinetics can be explained by the activity of small numbers of independent kinesin and dynein motors","authors":"Rawan M. Nowier,Christopher M. Johnson,J. Daniel Fenn,Anthony Brown,Peter Jung","doi":"10.1016/j.bpj.2026.09.016","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.016","url":null,"abstract":"Neurofilaments, which are intermediate filaments, are long flexible protein polymers that are transported bidirectionally along microtubule tracks in axons. Kymograph analysis of neurofilaments has revealed rapid intermittent movement with average run lengths that are consistent with the processive bouts of single motors, and frequent pauses and reversals that suggest rapid switching between opposing motors. To explore this, we used discrete stochastic models of kinesin and dynein motors to model neurofilament movement by teams of independent motors in axons. We describe an unbiased automated sampling algorithm to identify the numbers of kinesin and dynein motors required to match the range of pause times, run times, run lengths, and velocities for neurofilaments in a large dataset of ∼37,000 runs and pauses acquired with 30.3 millisecond resolution. We find that the diverse kinetic behavior of neurofilaments can be explained by the activity of 1-2 kinesin or dynein motors which interact indirectly via the mechanical forces they exert on the neurofilament cargo. Simultaneous engagement of opposing motors was rare in our simulations, indicating that the motile behavior can be explained by alternating kinesin and dynein activity without a competition between motors of opposite directionality.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"19 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148980626","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}

引用次数: 0

Cross-linking mass spectrometry: Workflow enhancements for mapping large-scale interactomes. 交联质谱：绘制大规模相互作用组的工作流程增强。

IF 3.7 3区生物学

Biophysical journal Pub Date : 2026-09-15 Epub Date: 2026-05-26 DOI: 10.1016/j.bpj.2026.05.033

Shenbaga Moorthy Balakrishnan, Taoufik Nedjadi, Rawiah Alsiary, Hifzur Rahman Ansari

{"title":"Cross-linking mass spectrometry: Workflow enhancements for mapping large-scale interactomes.","authors":"Shenbaga Moorthy Balakrishnan, Taoufik Nedjadi, Rawiah Alsiary, Hifzur Rahman Ansari","doi":"10.1016/j.bpj.2026.05.033","DOIUrl":"10.1016/j.bpj.2026.05.033","url":null,"abstract":"In vivo chemical cross-linking combined with mass spectrometry analysis (XL-MS) enables the direct capture of protein-protein interactions (PPIs) within their native cellular environment. This platform provides a unique capability to capture weak or transient interactions in near-native contexts, complementing other large-scale methods that may lose these associations during cell lysis or purification. The workflow involves selection of suitable chemical cross-linkers to stabilize PPIs in biological samples, ranging from organelles and cells to whole tissues. This is followed by careful sample preparation, high-resolution MS analysis, and computational identification of cross-linked peptides. Continuous advancements at each stage of this workflow have enhanced the sensitivity, throughput, and accuracy of the technique. A pivotal development has been the design of novel multifunctional cross-linkers featuring improved cell permeability, MS-cleavable sites, enrichment tags, and multisite reactivity. Furthermore, recent advances in MS instrumentation, data acquisition strategies, and computational software have increased the depth and reliability of cross-link identification. This review focuses on general workflows and recent innovations that accelerate the impact of in vivo XL-MS, highlighting experimental strategies for proteome-wide PPI mapping. The successful standardization of methodology would enable widespread acceptance and application of XL-MS to address diverse and complex biological questions.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"4941-4957"},"PeriodicalIF":3.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148026395","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}

引用次数: 0

Viral nucleosome-like particles show increased dynamic behavior and altered thermodynamic stability. 病毒核小体样颗粒表现出增加的动态行为和改变的热力学稳定性。

IF 3.7 3区生物学

Biophysical journal Pub Date : 2026-09-15 Epub Date: 2026-05-04 DOI: 10.1016/j.bpj.2026.04.036

Melanie E Melo, Jeff Wereszczynski

{"title":"Viral nucleosome-like particles show increased dynamic behavior and altered thermodynamic stability.","authors":"Melanie E Melo, Jeff Wereszczynski","doi":"10.1016/j.bpj.2026.04.036","DOIUrl":"10.1016/j.bpj.2026.04.036","url":null,"abstract":"DNA packaging imposes fundamental physical constraints on genomes across the tree of life. However, most of our mechanistic understanding of these processes comes from the eukaryotic nucleosome, where highly basic histones, along with their flexible tails, coordinate DNA compaction and gene accessibility. Large DNA viruses challenge this paradigm by assembling nucleosome-like particles with a divergent histone architecture. These viral assemblies lack full canonical histone tails, contain covalently fused domains linked by structured connectors, and exhibit altered surface electrostatics, features that collectively impose distinct biophysical properties on viral chromatin. Here, we use multi-microsecond all-atom molecular dynamics simulations to dissect how histone fusion, tail loss, and connector architecture reshape the structural and energetic behavior of the Melbournevirus nucleosome, a model system for studying viral chromatin organization. We find that viral systems exhibit elevated DNA unwrapping, weaker and more transient histone-DNA contacts, and localized flexibility at connector regions. Conformational adaptation at histone junctions partially offsets these effects, with structural shifts tuned to local DNA geometry during wrapping transitions. By capturing how nucleosome dynamics shift across time and sequence, our study provides a detailed view of how chromatin architecture can be reconfigured in viral nucleosome-like systems.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5360-5374"},"PeriodicalIF":3.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832899","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}

引用次数: 0

Protein function-conditioned language models for variant effect prediction and controllable design. 蛋白质功能条件语言模型的变异效应预测和可控设计。

IF 3.7 3区生物学

Biophysical journal Pub Date : 2026-09-15 Epub Date: 2026-05-14 DOI: 10.1016/j.bpj.2026.05.013

Shaowen Zhu, Yue Cao, Yihong Yang, Yang Shen

{"title":"Protein function-conditioned language models for variant effect prediction and controllable design.","authors":"Shaowen Zhu, Yue Cao, Yihong Yang, Yang Shen","doi":"10.1016/j.bpj.2026.05.013","DOIUrl":"10.1016/j.bpj.2026.05.013","url":null,"abstract":"Protein function-conditioned generative modeling can unify two core goals in protein engineering: predicting the effects of sequence variants and designing new sequences that satisfy functional constraints. We present a framework that conditions protein language modeling on molecular function semantics encoded from the Gene Ontology (GO) as a text-attributed directed acyclic graph. By embedding GO text and ontology topology, our function embedding captures relationships among functions and supports cross-function transfer. Function-conditioned meta-pretraining across diverse protein families further enables cross-family transfer before family-specific fine-tuning. Using these GO embeddings as conditioning context, we develop Func2Seq, a transformer-based autoregressive model of P(seq|func) that supports likelihood-based variant effect scoring and controllable sequence sampling. We further introduce Func2Prot, a joint sequence-structure extension that models P(seq, str|func) and enables direct backbone generation via a backbone-angle decoder. On a standard family-specific variant effect prediction benchmark, Func2Seq improves predictive performance over strong alignment-free and alignment-based baselines, and ablations show consistent gains from meta-pretraining when paired with family adaptation. A factor analysis indicates the largest improvements for small or low-diversity families. We also include enzyme fitness case studies to probe when joint sequence-structure modeling helps. For controllable design, we focus on the AT-rich interaction domain and show functional site-level constraint preservation while exploring globally novel sequence space, emphasizing function-critical binding regions and structural plausibility under appropriate evaluation pipelines.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5398-5409"},"PeriodicalIF":3.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939893","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}

引用次数: 0

Molecular Binding in Supramolecular Fibrillar Biomolecules 超分子纤维生物分子的分子结合

IF 3.4 3区生物学

Biophysical journal Pub Date : 2026-09-15 DOI: 10.1016/j.bpj.2026.09.019

Utana Umezaki,Cole Holladay,Zhi Mei Sonia He,Subhajit Chakraborty,Angel A. Martí

引用次数: 0

Effects of chromatin-lamina attachment on extra-long-range chromatin interactions. 染色质-薄片附着对超远程染色质相互作用的影响。

IF 3.7 3区生物学

Biophysical journal Pub Date : 2026-09-15 Epub Date: 2026-05-08 DOI: 10.1016/j.bpj.2026.05.011

Pourya Delafrouz, Hammad Farooq, Lin Du, Ao Ma, Jie Liang

{"title":"Effects of chromatin-lamina attachment on extra-long-range chromatin interactions.","authors":"Pourya Delafrouz, Hammad Farooq, Lin Du, Ao Ma, Jie Liang","doi":"10.1016/j.bpj.2026.05.011","DOIUrl":"10.1016/j.bpj.2026.05.011","url":null,"abstract":"The three-dimensional (3D) organization of the genome is strongly influenced by interactions between chromatin and lamin proteins at the nuclear envelope. Here, we investigate the role of lamina-associated domains (LADs) in shaping genome architecture using coarse-grained polymer models of mouse embryonic fibroblasts and embryonic stem cells. By integrating genome-wide LAD maps from DamID assays, we simulate chromatin conformations with and without LAD attachment. Incorporating LAD-lamina interactions reproduces the experimentally observed radial chromatin distribution and reveals that LADs induce extensive long-range (70-120 Mbp) chromatin contacts beyond typical loops and topologically associating domains (TADs). We describe these contacts in terms of two limiting geometric scenarios: LAD crowding, in which peripheral tethering increases the proximity of nearby non-LAD regions to LADs, and LAD anchoring, in which lamina-bound LADs constrain neighboring chromatin positions. LAD-induced interactions were especially prominent in chromatin regions lacking architectural proteins, such as CTCF, and were associated with lower gene density and reduced transcriptional activity. Together, these results suggest that LAD-lamina tethering reshapes long-range chromatin contact probabilities through boundary-driven effects and is associated with gene-poor, less transcriptionally active chromatin regions.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5387-5397"},"PeriodicalIF":3.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863482","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}

引用次数: 0

Energetic analysis of Na+/K+-ATPase using bond graphs Na+/K+- atp酶的键图能量分析

IF 3.4 3区生物学

Biophysical journal Pub Date : 2026-09-15 DOI: 10.1016/j.bpj.2026.09.014

Weiwei Ai,Peter J. Hunter,Michael Pan,David P. Nickerson

{"title":"Energetic analysis of Na+/K+-ATPase using bond graphs","authors":"Weiwei Ai,Peter J. Hunter,Michael Pan,David P. Nickerson","doi":"10.1016/j.bpj.2026.09.014","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.09.014","url":null,"abstract":"The sodium-potassium ATPase (NKA) accounts for 19–28% of the total ATP consumption in mammals and is critical for maintaining ion homeostasis. Understanding its energetic efficiency is essential for comprehending cellular physiology and pathophysiology. We develop bond graph models of the NKA that ensure thermodynamic consistency by enforcing conservation of mass, charge, and energy. A simplified 6-state model captures biophysics comparable to a 15-state model while remaining computationally tractable. Through detailed energetic analysis, we demonstrate that under physiological conditions for the mammalian cardiac cell, approximately 66% of the energy from ATP hydrolysis is stored as chemical energy in ion gradients, 12% as electrical energy in the membrane potential, and 22% is dissipated as heat, yielding an overall efficiency of ∼78%. We investigate how the free energy of ATP hydrolysis (ΔGMgATP), intracellular Na+, and extracellular K+ affect NKA efficiency and activity. A critical threshold exists at ΔGMgATP ≈ − 48 kJ/mol below which chemoelectrical transduction drops dramatically, consistent with NKA inhibition under ischemic conditions. The bond graph framework enables quantitative comparison of different NKA models and provides a systematic approach for analyzing ion pumps.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"15 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964335","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}

引用次数: 0

Hook stiffness as a mechanical switch for torque regulation in the bacterial flagellar motor. 钩刚度作为细菌鞭毛马达转矩调节的机械开关。

IF 3.7 3区生物学

Biophysical journal Pub Date : 2026-09-15 Epub Date: 2026-02-19 DOI: 10.1016/j.bpj.2026.02.018

Biswajit Das, Jianhua Xing, Ajeet K Sharma, Hao Ge

{"title":"Hook stiffness as a mechanical switch for torque regulation in the bacterial flagellar motor.","authors":"Biswajit Das, Jianhua Xing, Ajeet K Sharma, Hao Ge","doi":"10.1016/j.bpj.2026.02.018","DOIUrl":"10.1016/j.bpj.2026.02.018","url":null,"abstract":"The bacterial flagellar motor drives cell motility by rotating the flagellar filament and converting ion flux into mechanical work. At low counterclockwise (CCW) rotational speeds, the motor operates near the thermodynamic reversible limit, where torque remains nearly constant against rotation speed for an extended range. Earlier models based on thermodynamic reversibility predict qualitatively similar behavior in the clockwise (CW) direction, regardless of the underlying mechanism of torque generation. Structural studies further support this symmetry by showing that the torque-generation machinery in the two directions is essentially mirror reversed. However, single-molecule measurements reveal a striking asymmetry: CCW rotation shows a torque plateau, whereas CW rotation displays a linear decrease in torque with increasing speed. Here, we identify that this asymmetry has a mechanical origin in the rotation-dependent elasticity of the hook rather than in the motor's torque-generating units. In CCW rotation, the hook remains bent and compliant, maintaining a separation of timescales between motor stepping and load response and thereby preserving the torque plateau in the nearly thermodynamic reversible region. In CW rotation, the hook straightens and stiffens, collapsing the timescale separation and generating the observed linear torque-speed relationship. A mathematical model that varies only the hook's bending stiffness quantitatively reproduces the experimental torque-speed curves in both directions. These results resolve the long-standing puzzle of torque-speed asymmetry and identify hook elasticity as a key physical regulator of torque transmission in rotary molecular machines.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5243-5253"},"PeriodicalIF":3.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257116","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}

引用次数: 0

Jie Liang (1964-2024): Introduction to modeling biology at multiple scales: From macromolecules to cells, dedicated to Jie Liang. 梁洁（1964-2024）：多尺度生物学建模导论：从大分子到细胞，致力于梁洁。

IF 3.7 3区生物学

Biophysical journal Pub Date : 2026-09-15 Epub Date: 2026-09-05 DOI: 10.1016/j.bpj.2026.08.015

Ao Ma, Ruth Nussinov, Jianhan Chen, Jianhua Xing, Jie Xiao, Dong Xu, Meishan Lin, Pourya Delafrouz, Thomas Royston, Ke Tang, Bowei Ye, Jinfeng Zhang

引用次数: 0

Insights into fibrinogen mechanics under cyclic high-strain loading. 循环高应变载荷下纤维蛋白原力学的深入研究。

IF 3.7 3区生物学

Biophysical journal Pub Date : 2026-09-15 Epub Date: 2025-11-12 DOI: 10.1016/j.bpj.2025.11.017

Mayar Tarek Ibrahim, Sajjad Norouzi, Uma Paul, Sapun H Parekh, Pengyu Ren

{"title":"Insights into fibrinogen mechanics under cyclic high-strain loading.","authors":"Mayar Tarek Ibrahim, Sajjad Norouzi, Uma Paul, Sapun H Parekh, Pengyu Ren","doi":"10.1016/j.bpj.2025.11.017","DOIUrl":"10.1016/j.bpj.2025.11.017","url":null,"abstract":"Fibrinogen plays a central role in the physiological processes of blood coagulation and, unfortunately, ischemic stroke, where it is routinely exposed to mechanical forces. In this study, we employed atomistic molecular dynamics simulations to subject fibrinogen to three cycles of high-strain loading (∼17.5-27.5%) and unloading, enabling us to probe its mechanical response under cyclic stress. To capture the effects of pulling direction and structural asymmetry, we simulated the two different fibrinogen molecules present in the crystallographic unit cell. Forces were applied to the γ1 nodule of molecule 1 and the γ2 nodule of molecule 2 in opposite directions. The simulations revealed contrasting mechanical behaviors: the γ1 nodule exhibited greater extension with partial elasticity, whereas the β-sheet-rich γ2 nodule showed higher resistance but sustained irreversible structural damage. After force relaxation, both molecules retained residual strain (6.52-15.62% across independent replicas), confirming partial irreversibility. Anisotropic normal mode analysis further identified localized reductions in stiffness linked to unfolding of secondary structural elements, including β-sheets and α-helices. Complementary Kelvin-Voigt modeling of the unloading curves further quantified these effects, showing progressive reductions in the effective spring constant (Kspec) and dashpot coefficient (Cspec) across cycles. The model captured the viscoelastic relaxation dynamics. Collectively, these findings demonstrate that fibrinogen's cyclic response is shaped by both intrinsic structural heterogeneity, revealing viscoelastic behavior with important implications for clot formation and stroke pathogenesis.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"5064-5075"},"PeriodicalIF":3.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12930531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511447","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}

引用次数: 0