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":"<p><p>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.</p>","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}
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":"<p><p>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.</p>","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}
{"title":"Roles of chemical species transport and transformation in the biophysics of human pathophysiology.","authors":"Kazeem B Olanrewaju, Ashlee N Ford Versypt","doi":"10.1038/s44341-025-00025-3","DOIUrl":"10.1038/s44341-025-00025-3","url":null,"abstract":"<p><p>This review focuses on the roles of chemical species transport and biochemical and biophysical transformation within the gastrointestinal and immune systems and interactions with tissue structure and biomechanics in the mechanisms of pathophysiological conditions including gastrointestinal reflux disease and allergic responses. Combinations of biophysical and biochemical techniques are needed to unravel the complex interplay between transport and transformation to develop more effective interventions and ultimately improve patient outcomes.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12328227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819037","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}
{"title":"The role of dynamic reciprocity in 3D cell migration: connecting cell and matrix mechanics to migratory plasticity.","authors":"Jacob J Duggan, Ryan J Petrie","doi":"10.1038/s44341-025-00027-1","DOIUrl":"10.1038/s44341-025-00027-1","url":null,"abstract":"<p><p>While migratory cells can quickly change their mode of migration in complex three-dimensional environments, it is not clear why. Understanding the dynamic and reciprocal relationship migrating cells have with their microenvironments may help reveal why migratory plasticity, or mode-switching, is a common feature of eukaryotic cell motility. In this review, we discuss the physical and mechanical properties of cells and the environments they move through, and how those properties can influence each other. Given the dual role of the cytoskeleton in cell migration and cellular mechanics, we suggest that migratory plasticity derives from the necessity for the cell to maintain mechanical homeostasis in diverse physical environments.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017035","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}
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":"<p><p>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.</p>","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}
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":"<p><p>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.</p>","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}
Ayushi Agrawal, Yousef Javanmardi, Sara A Watson, Bianca Serwinski, Boris Djordjevic, Wenbin Li, Amir R Aref, Russell W Jenkins, Emad Moeendarbary
{"title":"Mechanical signatures in cancer metastasis.","authors":"Ayushi Agrawal, Yousef Javanmardi, Sara A Watson, Bianca Serwinski, Boris Djordjevic, Wenbin Li, Amir R Aref, Russell W Jenkins, Emad Moeendarbary","doi":"10.1038/s44341-024-00007-x","DOIUrl":"10.1038/s44341-024-00007-x","url":null,"abstract":"<p><p>The cancer metastatic cascade includes a series of mechanical barrier-crossing events, involving the physical movement of cancer cells from their primary location to a distant organ. This review describes the physical changes that influence tumour proliferation, progression, and metastasis. We identify potential mechanical signatures at every step of the metastatic cascade and discuss some latest mechanobiology-based therapeutic interventions to highlight the importance of interdisciplinary approaches in cancer diagnosis and treatment.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367196","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}
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":"<p><p>Mechanisms of blood clot contraction - platelet-driven fibrin network remodeling, are not fully understood. We developed a detailed computational <i>ClotDynaMo</i> model of fibrin network with activated platelets, whose clot contraction rate for normal 450,000/µl human platelets depends on serum viscosity <i>η</i>, platelet filopodia length <i>l</i>, and weakly depends on filopodia traction force <i>f</i> and filopodia extension-retraction speed <i>v</i>. Final clot volume is independent of <i>η</i>, but depends on <i>v</i>, <i>f</i> and <i>l</i>. Analysis of <i>ClotDynaMo</i> 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, <i>η</i> and <i>l</i>. The <i>ClotDynaMo</i> and continuum models can be extended to include red blood cells, variable platelet properties, and mechanics of fibrin network.</p>","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}
Nichaluk Leartprapun, Anton Deti, Brandon C Matthews, Ziqian Zeng, Nathaniel Hai, Seemantini K Nadkarni
{"title":"Speckle fluctuations reveal dynamics of microparticles in fibrin scaffolds in a model of bacterial infection.","authors":"Nichaluk Leartprapun, Anton Deti, Brandon C Matthews, Ziqian Zeng, Nathaniel Hai, Seemantini K Nadkarni","doi":"10.1038/s44341-025-00019-1","DOIUrl":"10.1038/s44341-025-00019-1","url":null,"abstract":"<p><p>Fibrin plays an important role in both immune response and pathogen virulence during bacterial infection. Pathogens such as staphylococci interact with fibrin through dynamic processes, involving binding, entrapment, and release from fibrin scaffolds, through which they experience an evolving cascade of nano- to microscale dynamics that span broad timescales. Yet, the biophysical dynamics that unfold between invading bacteria and host fibrin are not well understood. Here, we present a non-invasive optical approach based on speckle fluctuation to characterize the multiscale dynamics of microparticles in fibrin scaffolds. Using microparticles of varying sizes and surface chemistry to emulate spherical, non-motile bacterial cells, we demonstrate real-time monitoring of bacteria-fibrin interactions during fibrin clot formation and fibrinolysis in purified fibrins scaffolds and clinical plasma clots. Our approach circumvents the need for sophisticated position tracking equipment, making it potentially applicable to a broad range of experimental systems for biophysical investigation of bacteria-extracellular network interactions.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236434","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}
Roberto Alonso-Matilla, Paolo P Provenzano, David J Odde
{"title":"Physical principles and mechanisms of cell migration.","authors":"Roberto Alonso-Matilla, Paolo P Provenzano, David J Odde","doi":"10.1038/s44341-024-00008-w","DOIUrl":"10.1038/s44341-024-00008-w","url":null,"abstract":"<p><p>Cell migration is critical in processes such as developmental biology, wound healing, immune response, and cancer invasion/metastasis. Understanding its regulation is essential for developing targeted therapies in regenerative medicine, cancer treatment and immune modulation. This review examines cell migration mechanisms, highlighting fundamental physical principles, key molecular components, and cellular behaviors, identifying existing gaps in current knowledge, and suggesting potential directions for future research.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019728","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}