npj Biological Physics and Mechanics最新文献

Opening threshold and kinetics of the MscL mechanosensitive channel are regulated by its periplasmic loop. MscL机械敏感通道的开启阈值和动力学受其质周环调节。

npj Biological Physics and Mechanics Pub Date : 2026-01-01 Epub Date: 2026-09-04 DOI: 10.1038/s44341-026-00048-4

Kingsley C Duru, Paul Rohde, Hooman Hafezi, Omid Bavi, Navid Bavi, Boris Martinac

{"title":"Opening threshold and kinetics of the MscL mechanosensitive channel are regulated by its periplasmic loop.","authors":"Kingsley C Duru, Paul Rohde, Hooman Hafezi, Omid Bavi, Navid Bavi, Boris Martinac","doi":"10.1038/s44341-026-00048-4","DOIUrl":"10.1038/s44341-026-00048-4","url":null,"abstract":"Mechanosensitive channels of large conductance (MscL) protect bacteria from hypo-osmotic stress by opening a large pore in response to membrane tension. The transmembrane TM1 and TM2 helices together with the N-terminal amphipathic helix function as the primary force-sensing structural domains, whereas the role of the periplasmic loop in the channel gating remains poorly understood. Using experimental and computational approaches, our study demonstrates that mutating the loop residues (A64, Q65, G66, D67) or inserting a four-glycine flexible hinge at D67 site modified the properties of the channel recorded in giant E. coli spheroplasts and liposomes composed of azolectin or negatively charged lipids. Extending the periplasmic loop disrupted mechanical force transmission, reducing channel sensitivity to applied tension. Q65R channel mutant exhibited increased sensitivity in azolectin liposomes that was reduced in negatively charged liposomes and spheroplast membranes. The Q65E mutant showed decreased sensitivity across all preparations tested and exhibited channel flickering in negatively charged liposomes. Molecular dynamics simulations revealed that Q65E produced larger but more structurally restricted conformational changes, whereas wild-type MscL and Q65R exhibited rapid and extensive pore opening over a shorter timeframe. Our findings establish the periplasmic loop as a structural domain fine-tuning MscL gating through electrostatic interactions with surrounding lipids.","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"3 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A large-scale balloon model of confluent cells validates stress inference from geometry. 融合细胞的大尺度气球模型验证了几何应力推断。

npj Biological Physics and Mechanics Pub Date : 2026-01-01 Epub Date: 2026-01-07 DOI: 10.1038/s44341-025-00031-5

Joseph K Hall, Yuqing Deng, Konstantinos Kontodimas, Hadi Nia, Xaralabos Varelas, Kenneth R Lutchen, Jason Bates, Béla Suki

{"title":"A large-scale balloon model of confluent cells validates stress inference from geometry.","authors":"Joseph K Hall, Yuqing Deng, Konstantinos Kontodimas, Hadi Nia, Xaralabos Varelas, Kenneth R Lutchen, Jason Bates, Béla Suki","doi":"10.1038/s44341-025-00031-5","DOIUrl":"10.1038/s44341-025-00031-5","url":null,"abstract":"The mechanical environment surrounding cells influences their behavior. Multiple methods have been developed to measure local mechanics with mechanical perturbation, which is invasive. For sheets of confluent cells, the geometry of the boundaries of the cells can be used to estimate the local membrane tension and internal cell pressure through stress inference (SI), which is image-based and therefore non-invasive. SI is sensitive to noise and has not been validated in a physical system using a direct pressure measurement. We developed a large-scale model of confluent cells using densely-packed balloons with interior pressure sensors to allow for simultaneous measurement of pressure and geometry. We also developed a new SI method which resulted in a correlation coefficient >0.8 with the balloon model, less noise sensitivity in computational models, and measured pressure change in red onion epithelial cells. These results demonstrate the validity and utility of SI in multiscale physical and computational applications.","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"3 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polarization increases nuclear stiffness in macrophages despite reduction in lamin A/C levels. 极化增加巨噬细胞的核硬度，尽管降低了层粘胶蛋白A/C水平。

npj Biological Physics and Mechanics Pub Date : 2026-01-01 Epub Date: 2026-06-01 DOI: 10.1038/s44341-026-00038-6

Margaret A Elpers, Jacob Odell, Sarah J Henretta, Tong Shu, Yogeshwari Sanjayrao Ambekar, Hassan Saadi, Graeme F Woodworth, Warren R Zipfel, Giuliano Scarcelli, Liam J Holt, Jan Lammerding

{"title":"Polarization increases nuclear stiffness in macrophages despite reduction in lamin A/C levels.","authors":"Margaret A Elpers, Jacob Odell, Sarah J Henretta, Tong Shu, Yogeshwari Sanjayrao Ambekar, Hassan Saadi, Graeme F Woodworth, Warren R Zipfel, Giuliano Scarcelli, Liam J Holt, Jan Lammerding","doi":"10.1038/s44341-026-00038-6","DOIUrl":"10.1038/s44341-026-00038-6","url":null,"abstract":"Macrophages are innate immune cells contributing to tissue homeostasis and various pathologies. Signals from their environment can lead macrophages to adapt distinct functional phenotypes, a process called polarization. Because macrophages have been previously shown to degrade the nuclear envelope proteins lamin A/C upon pro-inflammatory polarization, and lamins are considered key determinants of nuclear deformability, we aimed to address the effect of pro-inflammatory stimulation on nuclear mechanics. We present the surprising finding that polarized bone marrow-derived macrophages have less deformable nuclei than unpolarized macrophages, despite their reduced lamin A/C levels. Furthermore, pro-inflammatory macrophages exhibited altered chromatin dynamics relative to unpolarized macrophages, including redistribution of trimethylated histone H3K9 (H3K9me3) from the nuclear periphery to the interior and increased chromatin compaction. Our findings suggest a model in which pro-inflammatory stimulation of macrophages induces chromatin changes that drive nuclear stiffening, and that in these cells, chromatin, rather than the nuclear lamina, is the major driver for resisting nuclear deformation. These findings may have functional relevance for the physiological function of polarized macrophages, as the mechanical properties of the nucleus can influence how these cells adapt and respond to their environments in the context of cell migration or inflammatory disease pathologies.","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"3 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13229938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148166427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stemless molecular beacon probes for single-molecule detection of supercoil-induced DNA denaturation. 用于超线圈诱导DNA变性单分子检测的无茎分子信标探针。

npj Biological Physics and Mechanics Pub Date : 2026-01-01 Epub Date: 2026-01-07 DOI: 10.1038/s44341-025-00032-4

Cynthia Shaheen, Bianca Caminada, Alexis Hilts, Ruby Wei, Jay Botham, Rebecca Johnson, Nane Vardanyan, Eric Boateng, Sabrina Leslie

{"title":"Stemless molecular beacon probes for single-molecule detection of supercoil-induced DNA denaturation.","authors":"Cynthia Shaheen, Bianca Caminada, Alexis Hilts, Ruby Wei, Jay Botham, Rebecca Johnson, Nane Vardanyan, Eric Boateng, Sabrina Leslie","doi":"10.1038/s44341-025-00032-4","DOIUrl":"10.1038/s44341-025-00032-4","url":null,"abstract":"While the formation of single-stranded regions in DNA plays important roles in processes such as replication, repair, and transcription, the underlying mechanics and kinetics of these structures are not well understood. Here, we combine single-molecule Convex Lens-induced Confinement (CLiC) microscopy with stemless molecular beacons to detect and study correlations in the formation of multiple single-stranded regions within plasmids in suspended solution conditions. We demonstrate that negative supercoiling not only increases denaturation of these sites, but also augments oligo-plasmid binding interactions. The observed denaturation disagrees with theoretical predictions stemming from equilibrium thermodynamics, suggesting the structures may form metastable states. To our knowledge, this is the first single-molecule study of plasmids in suspended solution conditions to make measurements correlating the formation of multiple single-stranded regions within the same plasmid. Beyond DNA mechanics, these methods have the potential to enable insights in a broad range of fields, such as informing the development of therapeutics sensitive to DNA and RNA structure.","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"3 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Roles of chemical species transport and transformation in the biophysics of human pathophysiology. 化学物质转运和转化在人体病理生理生物物理中的作用。

npj Biological Physics and Mechanics Pub Date : 2025-01-01 Epub Date: 2025-08-06 DOI: 10.1038/s44341-025-00025-3

Kazeem B Olanrewaju, Ashlee N Ford Versypt

引用次数: 0

Deformable registration and generative modelling of aortic anatomies by auto-decoders and neural ODEs. 利用自动解码器和神经ode进行主动脉解剖的形变配准和生成建模。

npj Biological Physics and Mechanics Pub Date : 2025-01-01 Epub Date: 2025-12-03 DOI: 10.1038/s44341-025-00029-z

Riccardo Tenderini, Luca Pegolotti, Fanwei Kong, Stefano Pagani, Francesco Regazzoni, Alison L Marsden, Simone Deparis

{"title":"Deformable registration and generative modelling of aortic anatomies by auto-decoders and neural ODEs.","authors":"Riccardo Tenderini, Luca Pegolotti, Fanwei Kong, Stefano Pagani, Francesco Regazzoni, Alison L Marsden, Simone Deparis","doi":"10.1038/s44341-025-00029-z","DOIUrl":"10.1038/s44341-025-00029-z","url":null,"abstract":"Accurate registration of vascular shapes is essential for comparing anatomical geometries, extracting reliable measurements, and generating realistic models in cardiovascular research. Conventional surface registration methods often face limitations in efficiency, scalability, and generalization across shape cohorts. In this work, we present AD-SVFD, a deep learning framework that simultaneously performs deformable registration of vascular geometries to a pre-defined reference anatomy and enables the synthesis of new shapes. AD-SVFD represents each geometry as a point cloud and models ambient deformations as solutions at unit time of ordinary differential equations (ODEs), whose time-independent right-hand sides are parameterized by neural networks. Registration is optimized by minimizing the Chamfer distance between deformed and reference geometries, while shape generation is achieved by integrating the ODE backward in time from sampled latent codes. A distinctive auto-decoder architecture associates each anatomy with a low-dimensional embedding, jointly optimized with the network parameters during training, and fine-tuned at inference, reducing computational overhead. Numerical experiments on healthy aortic anatomies demonstrate the capability of AD-SVFD to yield accurate approximations at competitive computational costs. Compared to existing approaches, our model offers an efficient, unified framework for processing multiple shapes and robustly generating plausible geometries.","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12675294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tissue-dependent mechanosensing by cells derived from human tumors. 来源于人类肿瘤细胞的组织依赖性机械传感。

npj Biological Physics and Mechanics Pub Date : 2025-01-01 Epub Date: 2025-08-06 DOI: 10.1038/s44341-025-00023-5

Kshitiz Parihar, Jonathan Nukpezah, Daniel V Iwamoto, Katrina Cruz, Fitzroy J Byfield, LiKang Chin, Maria E Murray, Melissa G Mendez, Anne S van Oosten, Anne Herrmann, Elisabeth E Charrier, Peter A Galie, Megan Donlick, Tongkeun Lee, Paul A Janmey, Ravi Radhakrishnan

{"title":"Tissue-dependent mechanosensing by cells derived from human tumors.","authors":"Kshitiz Parihar, Jonathan Nukpezah, Daniel V Iwamoto, Katrina Cruz, Fitzroy J Byfield, LiKang Chin, Maria E Murray, Melissa G Mendez, Anne S van Oosten, Anne Herrmann, Elisabeth E Charrier, Peter A Galie, Megan Donlick, Tongkeun Lee, Paul A Janmey, Ravi Radhakrishnan","doi":"10.1038/s44341-025-00023-5","DOIUrl":"10.1038/s44341-025-00023-5","url":null,"abstract":"Alterations of the extracellular matrix (ECM), including both mechanical (such as stiffening of the ECM) and chemical (such as variation of adhesion proteins and deposition of hyaluronic acid (HA)) changes, in malignant tissues have been shown to mediate tumor progression. To survey how cells from different tissue types respond to various changes in ECM mechanics and composition, we measured physical characteristics (adherent area, shape, cell stiffness, and cell speed) of 25 cancer and 5 non-tumorigenic cell lines on 7 different substrate conditions. Our results indicate substantial heterogeneity in how cell mechanics changes within and across tissue types in response to mechanosensitive and chemosensitive changes in ECM. The analysis also underscores the role of HA in ECM with some cell lines showing changes in cell mechanics in response to presence of HA in soft substrate that are similar to those observed on stiff substrates. This pan-cancer investigation also highlights the importance of tissue-type and cell line specificity for inferences made based on comparison between physical properties of cancer and normal cells. Lastly, using unsupervised machine learning, we identify phenotypic classes that characterize the physical plasticity, i.e., the distribution of physical feature values attainable, of a particular cell type in response to different ECM-based conditions.","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12328224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of dynamic reciprocity in 3D cell migration: connecting cell and matrix mechanics to migratory plasticity. 动态互易在三维细胞迁移中的作用：将细胞和基质力学与迁移塑性联系起来。

npj Biological Physics and Mechanics Pub Date : 2025-01-01 Epub Date: 2025-09-03 DOI: 10.1038/s44341-025-00027-1

Jacob J Duggan, Ryan J Petrie

引用次数: 0

Mechanical signatures in cancer metastasis. 癌症转移的机械特征。

npj Biological Physics and Mechanics Pub Date : 2025-01-01 Epub Date: 2025-02-04 DOI: 10.1038/s44341-024-00007-x

Ayushi Agrawal, Yousef Javanmardi, Sara A Watson, Bianca Serwinski, Boris Djordjevic, Wenbin Li, Amir R Aref, Russell W Jenkins, Emad Moeendarbary

引用次数: 0

Exploring effects of platelet contractility on the kinetics, thermodynamics, and mechanisms of fibrin clot contraction. 探讨血小板收缩对纤维蛋白凝块收缩的动力学、热力学和机制的影响。

npj Biological Physics and Mechanics Pub Date : 2025-01-01 Epub Date: 2025-02-24 DOI: 10.1038/s44341-025-00011-9

Evgenii Kliuchnikov, Alina D Peshkova, Minh Quan Vo, Kenneth A Marx, Rustem I Litvinov, John W Weisel, Prashant K Purohit, Valeri Barsegov

{"title":"Exploring effects of platelet contractility on the kinetics, thermodynamics, and mechanisms of fibrin clot contraction.","authors":"Evgenii Kliuchnikov, Alina D Peshkova, Minh Quan Vo, Kenneth A Marx, Rustem I Litvinov, John W Weisel, Prashant K Purohit, Valeri Barsegov","doi":"10.1038/s44341-025-00011-9","DOIUrl":"10.1038/s44341-025-00011-9","url":null,"abstract":"Mechanisms of blood clot contraction - platelet-driven fibrin network remodeling, are not fully understood. We developed a detailed computational ClotDynaMo model of fibrin network with activated platelets, whose clot contraction rate for normal 450,000/µl human platelets depends on serum viscosity η, platelet filopodia length l, and weakly depends on filopodia traction force f and filopodia extension-retraction speed v. Final clot volume is independent of η, but depends on v, f and l. Analysis of ClotDynaMo output revealed a 2.24 TJ/mol clot contraction free energy change, with ~67% entropy and ~33% internal energy changes. The results illuminate the \"optimal contraction principle\" that maximizes volume change while minimizing energy cost. An 8-chain continuum model of polymer elasticity containing platelet forces, captures clot contractility as a function of platelet count, η and l. The ClotDynaMo and continuum models can be extended to include red blood cells, variable platelet properties, and mechanics of fibrin network.","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0