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}
Gia Kang, Eng Kuan Moo, Rohan Banton, Oren E Petel, Andrew R Harris
{"title":"Cellular mechanisms of traumatic brain injury.","authors":"Gia Kang, Eng Kuan Moo, Rohan Banton, Oren E Petel, Andrew R Harris","doi":"10.1038/s44341-025-00020-8","DOIUrl":"10.1038/s44341-025-00020-8","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) is an acute injury with immediate and medium-term symptom presentation. However, our mechanistic understanding of mTBI and how mechanical loading of soft cellular tissues leads to injury is limited. The aim of this review is to introduce this interdisciplinary field to non-experts and provide an overview of our current understanding of how mechanical trauma contributes to cellular injury. Here, we compare the significance of various measures of mechanical loading including strain magnitude, strain rate, loading mode, and frequency, and their relative significance for cell and tissue injury in <i>in vitro</i> and <i>ex vivo</i> experimental models reported in the literature. Interestingly, while it is difficult to define a precise injury threshold value based on strain magnitude alone, cellular injury is commonly observed at strain rates of >0.1 s<sup>-1</sup>, higher than rates observed in many normal cell functions (< 0.01 s<sup>-1</sup>). We explore the role of the plasma membrane, cytoskeleton, and specialized structures in maintaining cell integrity during traumatic injury.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236433","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}
Ronja Rappold, Konstantinos Kalogeropoulos, Gianna La Regina, Ulrich Auf dem Keller, Emma Slack, Viola Vogel
{"title":"Relaxation of mucosal fibronectin fibers in late gut inflammation following neutrophil infiltration in mice.","authors":"Ronja Rappold, Konstantinos Kalogeropoulos, Gianna La Regina, Ulrich Auf dem Keller, Emma Slack, Viola Vogel","doi":"10.1038/s44341-024-00006-y","DOIUrl":"10.1038/s44341-024-00006-y","url":null,"abstract":"<p><p>The continuously remodeled extracellular matrix (ECM) plays a pivotal role in gastrointestinal health and disease, yet its precise functions remain elusive. In this study, we employed laser capture microdissection combined with low-input proteomics to investigate ECM remodeling during <i>Salmonella</i>-driven inflammation. To complement this, we probed how fibronectin fiber tension is altered using a mechanosensitive peptide probe. While fibronectin fibers in healthy intestinal tissue are typically stretched, many lose their tension in intestinal smooth muscles only hours after infection, despite the absence of bacteria in that area. In contrast, within the mucosa, where <i>Salmonella</i> is present starting 12 h post infection, fibronectin fiber relaxation occurred exclusively during late-stage infection at 72 h and was localized to already existing clusters of infiltrated neutrophils. Using N-terminomics, we identified three new cleavage sites in fibronectin in the inflamed cecum. The unique, tissue layer-specific changes in the molecular compositions and ECM fiber tension revealed herein might trigger new therapeutic strategies to fight acute intestinal inflammation.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367198","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 extracellular matrix viscoelasticity in development and disease.","authors":"Olivia Courbot, Alberto Elosegui-Artola","doi":"10.1038/s44341-025-00014-6","DOIUrl":"10.1038/s44341-025-00014-6","url":null,"abstract":"<p><p>For several decades, research has studied the influence of the extracellular matrix (ECM) mechanical properties in cell response, primarily emphasising its elasticity as the main determinant of cell and tissue behaviour. However, the ECM is not purely elastic; it is viscoelastic. ECM viscoelasticity has now emerged as a major regulator of collective cell dynamics. This review highlights recent findings on the role of ECM viscoelasticity in development and pathology.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797469","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}
Yufei Wu, Pei-Hsun Wu, Allison Chambliss, Denis Wirtz, Sean X Sun
{"title":"Unifying fragmented perspectives with additive deep learning for high-dimensional models from partial faceted datasets.","authors":"Yufei Wu, Pei-Hsun Wu, Allison Chambliss, Denis Wirtz, Sean X Sun","doi":"10.1038/s44341-025-00009-3","DOIUrl":"10.1038/s44341-025-00009-3","url":null,"abstract":"<p><p>Biological systems are complex networks where measurable functions emerge from interactions among thousands of components. Many studies aim to link biological function with molecular elements, yet quantifying their contributions simultaneously remains challenging, especially at the single-cell level. We propose a machine-learning approach that integrates faceted data subsets to reconstruct a complete view of the system using conditional distributions. We develop both polynomial regression and neural network models, validated with two examples: a mechanical spring network under external forces and an 8-dimensional biological network involving the senescence marker P53, using single-cell data. Our results demonstrate successful system reconstruction from partial datasets, with predictive accuracy improving as more variables are measured. This approach offers a systematic method to integrate fragmented experimental data, enabling unbiased and holistic modeling of complex biological functions.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517742","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":"Mechanobiology in the eye.","authors":"C Ross Ethier, Samuel Herberg","doi":"10.1038/s44341-025-00022-6","DOIUrl":"10.1038/s44341-025-00022-6","url":null,"abstract":"<p><p>The eye presents a very dynamic biomechanical environment, and thus ocular cells must be highly mechanosensitive and mechanoresponsive. Moreover, defects in mechanobiological pathways contribute to a number of sight-threatening ocular diseases, highlighting the importance of ocular mechanobiology. We here give a concise overview of the mechanobiology of ocular cells in the lens and cornea (and how mechanobiology plays a role in associated pathologies in these tissues), before providing a detailed review of the mechanobiology of the common blinding disease, glaucoma. Mechanical stimuli are intimately linked with the pathology of glaucoma, both in terms of altered homeostasis of the eye's internal pressure control system and in the response of neural cells to elevated pressure in the eye. A complex array of mechanosensory elements (stretch-activated ion channels, integrins, G protein-coupled receptors) work together with intersecting networks of mechanotransducing pathways in cells of both the posterior and anterior eye in glaucoma. Despite intense research efforts over the past decades, much remains unknown about the mechanobiology of glaucoma. Continued investigation of glaucomatous mechanobiology is important, as it may reveal novel targets for treating this challenging disease.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577535","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 synergistic potential of mechanotherapy and sonopermeation to enhance cancer treatment effectiveness.","authors":"Constantina Neophytou, Triantafyllos Stylianopoulos, Fotios Mpekris","doi":"10.1038/s44341-025-00017-3","DOIUrl":"https://doi.org/10.1038/s44341-025-00017-3","url":null,"abstract":"<p><p>Inefficient drug delivery in tumors, especially in desmoplastic cancers, arises from blood vessel collapse due to tumor stiffening and mechanical compression. Vessel collapse also leads to hypoxia, immune evasion, and metastasis, reducing treatment efficacy. Mechanotherapeutics and ultrasound sonopermeation, which address tumor stiffness and enhance vessel permeability, respectively, show promise in restoring tumor microenvironment abnormalities and improving drug delivery. This perspective highlights their independent and combined potential to optimize cancer therapy.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997233","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}