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}
Marie Floryan, Elena Cambria, Adriana Blazeski, Mark F Coughlin, Zhengpeng Wan, Giovanni Offeddu, Vinayak Vinayak, Aayush Kant, Jordan Whisler, Vivek Shenoy, Roger D Kamm
{"title":"Long-term physiological flow rescues regressed microvascular networks and increases their longevity.","authors":"Marie Floryan, Elena Cambria, Adriana Blazeski, Mark F Coughlin, Zhengpeng Wan, Giovanni Offeddu, Vinayak Vinayak, Aayush Kant, Jordan Whisler, Vivek Shenoy, Roger D Kamm","doi":"10.1038/s44341-025-00028-0","DOIUrl":"10.1038/s44341-025-00028-0","url":null,"abstract":"<p><p>The incorporation of a functional perfusable microvascular network (MVN) is a common requirement for most organ on-chip-models. Long-term perfusion of MVNs is often required for the maturation of organ phenotypes and disease pathologies and to model the transport of cells and drugs entering organs. Here, we use a microfluidic pump to apply continuous, recirculating physiological flow through self-assembler microvascular networks. In our microphysiological system (MPS), we observe that flow can recover perfusion in regressed MVNs and maintain perfusable MVNs for at least 51 days. Throughout the 51 days, however, the MVNs are continuously remodeling to align with the direction of bulk flow and only appear to attain morphological homeostasis with the use of maintenance medium without growth factors. We observed that the flow resistance of the MVNs decreases over time, and using a computational model, we show that stable vessels have higher flow rates and velocities compared to regressing vessels. Cytokine analysis suggests that static conditions generate an inflammatory state, and that continuous flow reduces inflammation over an extended period. Finally, through bulk RNA sequencing we identify that both the endothelial and fibroblast cells are actively engaged in flow-induced vascular and matrix remodeling and that these effects persist for at least 2 weeks. This MPS can be applied to study hemodynamically driven processes, such as metastatic dissemination or drug distribution, or to model long-term diseases previously not captured by MPS, such as chronic inflammation or aging-associated diseases.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12586172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461134","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}
Kathryn Regan, Lauren Castle, Robert LeBourdais, Abdulrahman Kobayter, Linzheng Shi, Winita Wangsrikhun, Gabrielle Grifno, Rohin Banerji, Athanasios Batgidis, Béla Suki, Hadi T Nia
{"title":"Micromechanics of lung capillaries across mouse lifespan and in positive- vs negative-pressure ventilation.","authors":"Kathryn Regan, Lauren Castle, Robert LeBourdais, Abdulrahman Kobayter, Linzheng Shi, Winita Wangsrikhun, Gabrielle Grifno, Rohin Banerji, Athanasios Batgidis, Béla Suki, Hadi T Nia","doi":"10.1038/s44341-025-00026-2","DOIUrl":"10.1038/s44341-025-00026-2","url":null,"abstract":"<p><p>The lung undergoes continuous remodeling throughout normal development and aging, including changes to alveolar and capillary structure and function. While histological methods allow for static analysis of these age-related changes, characterizing the changes that occur in response to mechanical stimuli remains difficult, particularly over a dynamic, physiologically relevant range in a functioning lung. Alveolar and capillary distension - the change in diameter of alveoli and capillaries, respectively, in response to pressure changes - is one such process, where dynamically controlling and monitoring the diameter of the same capillary or alveolus is essential to inferring its mechanical properties. We overcome these limitations by utilizing the recently developed crystal ribcage to image the alveoli and vasculature of a functional mouse lung across the lifespan in postnatal (6-7 days), young adult (12-18 weeks), and aged (20+ months) mice. Using a range of biologically relevant vascular (0-15 cmH<sub>2</sub>O) and transpulmonary (3-12 cm H<sub>2</sub>O) pressures, we directly quantify vascular and alveolar distention in the functional lung as we precisely adjust pulmonary pressures. Our results show differences in age-related alveolar and vascular distensibility: when we increase transpulmonary alveolar or vascular pressure, vessels in postnatal lungs expand less and undergo less radial and axial strain under each respective pressure type, suggesting stiffer capillaries than in older lungs. However, while vessels in young adult and aged lungs respond similarly to variations in vascular pressure, differences in elasticity start to emerge at the alveolar scale in response to transpulmonary alveolar pressure changes. Our results further indicate that differing effects of ventilation mode (i.e., positive vs. negative) present themselves at the capillary level, with vessels under positive pressure undergoing more compression than when under negative-pressure conditions. These findings contribute both to the understanding of the functional changes that occur within the lung across the lifespan, as well as to the debate of ventilation effects on lung microphysiology.</p>","PeriodicalId":501703,"journal":{"name":"npj Biological Physics and Mechanics","volume":"2 1","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017052","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}