Kshitiz Parihar , Seung-Hyun B. Ko , Ryan P. Bradley , Phillip Taylor , N. Ramakrishnan , Tobias Baumgart , Wei Guo , Valerie M. Weaver , Paul A. Janmey , Ravi Radhakrishnan
{"title":"Asymmetric crowders and membrane morphology at the nexus of intracellular trafficking and oncology","authors":"Kshitiz Parihar , Seung-Hyun B. Ko , Ryan P. Bradley , Phillip Taylor , N. Ramakrishnan , Tobias Baumgart , Wei Guo , Valerie M. Weaver , Paul A. Janmey , Ravi Radhakrishnan","doi":"10.1016/j.mbm.2024.100071","DOIUrl":"https://doi.org/10.1016/j.mbm.2024.100071","url":null,"abstract":"<div><p>A definitive understanding of the interplay between protein binding/migration and membrane curvature evolution is emerging but needs further study. The mechanisms defining such phenomena are critical to intracellular transport and trafficking of proteins. Among trafficking modalities, exosomes have drawn attention in cancer research as these nano-sized naturally occurring vehicles are implicated in intercellular communication in the tumor microenvironment, suppressing anti-tumor immunity and preparing the metastatic niche for progression. A significant question in the field is how the release and composition of tumor exosomes are regulated. In this perspective article, we explore how physical factors such as geometry and tissue mechanics regulate cell cortical tension to influence exosome production by co-opting the biophysics as well as the signaling dynamics of intracellular trafficking pathways and how these exosomes contribute to the suppression of anti-tumor immunity and promote metastasis. We describe a multiscale modeling approach whose impact goes beyond the fundamental investigation of specific cellular processes toward actual clinical translation. Exosomal mechanisms are critical to developing and approving liquid biopsy technologies, poised to transform future non-invasive, longitudinal profiling of evolving tumors and resistance to cancer therapies to bring us one step closer to the promise of personalized medicine.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 3","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000342/pdfft?md5=82f74f64557cd0e9b08dee1c94f412b1&pid=1-s2.0-S2949907024000342-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924556","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}
Si-Yu Hu , Chun-Dong Xue , Yong-Jiang Li , Shen Li , Zheng-Nan Gao , Kai-Rong Qin
{"title":"Microfluidic investigation for shear-stress-mediated repair of dysglycemia-induced endothelial cell damage","authors":"Si-Yu Hu , Chun-Dong Xue , Yong-Jiang Li , Shen Li , Zheng-Nan Gao , Kai-Rong Qin","doi":"10.1016/j.mbm.2024.100069","DOIUrl":"https://doi.org/10.1016/j.mbm.2024.100069","url":null,"abstract":"<div><p>Dysglycemia causes arterial endothelial damage, which is an early critical event in vascular complications for diabetes patients. Physiologically, moderate shear stress (SS) helps maintain endothelial cell health and normal function. Reactive oxygen species (ROS) and calcium ions (Ca<sup>2+</sup>) signals are involved in dysglycemia-induced endothelial dysfunction and are also implicated in SS-mediated regulation of endothelial cell function. Therefore, it is urgent to establish <em>in vitro</em> models for studying endothelial biomechanics and mechanobiology, aiming to seek interventions that utilize appropriate SS to delay or reverse endothelial dysfunction. Microfluidic technology, as a novel approach, makes it possible to replicate blood glucose environment and accurate pulsatile SS <em>in vitro</em>. Here, we reviewed the progress of microfluidic systems used for SS-mediated repair of dysglycemia-induced endothelial cell damage (ECD), revealing the crucial roles of ROS and Ca<sup>2+</sup> during the processes. It holds significant implications for finding appropriate mechanical intervention methods, such as exercise training, to prevent and treat cardiovascular complications in diabetes.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 3","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000329/pdfft?md5=a518abb78cf0a5c00975a90358021bba&pid=1-s2.0-S2949907024000329-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140895022","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}
Wenqiang Du , Ashkan Novin , Yamin Liu , Junaid Afzal , Shaofei Liu , Yasir Suhail , Kshitiz
{"title":"Stable and oscillatory hypoxia differentially regulate invasibility of breast cancer associated fibroblasts","authors":"Wenqiang Du , Ashkan Novin , Yamin Liu , Junaid Afzal , Shaofei Liu , Yasir Suhail , Kshitiz","doi":"10.1016/j.mbm.2024.100070","DOIUrl":"https://doi.org/10.1016/j.mbm.2024.100070","url":null,"abstract":"<div><p>As local regions in the tumor outstrip their oxygen supply, hypoxia can develop, affecting not only the cancer cells, but also other cells in the microenvironment, including cancer associated fibroblasts (CAFs). Hypoxia is also not necessarily stable over time, and can fluctuate or oscillate. Hypoxia Inducible Factor-1 is the master regulator of cellular response to hypoxia, and can also exhibit oscillations in its activity. To understand how stable, and fluctuating hypoxia influence breast CAFs, we measured changes in gene expression in CAFs in normoxia, hypoxia, and oscillatory hypoxia, as well as measured change in their capacity to resist, or assist breast cancer invasion. We show that hypoxia has a profound effect on breast CAFs causing activation of key pathways associated with fibroblast activation, but reduce myofibroblast activation and traction force generation. We also found that oscillatory hypoxia, while expectedly resulted in a “sub-hypoxic” response in gene expression, it resulted in specific activation of pathways associated with actin polymerization and actomyosin maturation. Using traction force microscopy, and a nanopatterned stromal invasion assay, we show that oscillatory hypoxia increases contractile force generation vs stable hypoxia, and increases heterogeneity in force generation response, while also additively enhancing invasibility of CAFs to MDA-MB-231 invasion. Our data show that stable and unstable hypoxia can regulate many mechnobiological characteristics of CAFs, and can contribute to transformation of CAFs to assist cancer dissemination and onset of metastasis.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 3","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000330/pdfft?md5=3b091afca74e4a263697c398a9097d07&pid=1-s2.0-S2949907024000330-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140950603","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}
Brian Chesney Quartey , Gabriella Torres , Mei ElGindi , Aseel Alatoom , Jiranuwat Sapudom , Jeremy CM Teo
{"title":"Tug of war: Understanding the dynamic interplay of tumor biomechanical environment on dendritic cell function","authors":"Brian Chesney Quartey , Gabriella Torres , Mei ElGindi , Aseel Alatoom , Jiranuwat Sapudom , Jeremy CM Teo","doi":"10.1016/j.mbm.2024.100068","DOIUrl":"https://doi.org/10.1016/j.mbm.2024.100068","url":null,"abstract":"<div><p>Dendritic cells (DCs) play a pivotal role in bridging the innate and adaptive immune systems. From their immature state, scavenging tissue for foreign antigens to uptake, then maturation, to their trafficking to lymph nodes for antigen presentation, these cells are exposed to various forms of mechanical forces. Particularly, in the tumor microenvironment, it is widely known that microenvironmental biomechanical cues are heightened. The source of these forces arises from cell-to-extracellular matrix (ECM) and cell-to-cell interactions, as well as being exposed to increased microenvironmental pressures and fluid shear forces typical of tumors. DCs then integrate these forces, influencing their immune functions through mechanotransduction. This aspect of DC biology holds alternative, but important clues to understanding suppressed/altered DC responses in tumors, or allow the artificial enhancement of DCs for therapeutic purposes. This review discusses the current understanding of DC mechanobiology from the perspectives of DCs as sensors of mechanical forces and providers of mechanical forces.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 3","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000317/pdfft?md5=29269c7dc3e815e4976547bdca32e66d&pid=1-s2.0-S2949907024000317-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140824693","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 motor-clutch model in mechanobiology and mechanomedicine","authors":"Zhao Xu , Feng Xu , Bo Cheng","doi":"10.1016/j.mbm.2024.100067","DOIUrl":"10.1016/j.mbm.2024.100067","url":null,"abstract":"<div><p>Cellular behaviors such as migration, spreading, and differentiation arise from the interplay of cell–matrix interactions. The comprehension of this interplay has been advanced by the motor-clutch model, a theoretical framework that captures the binding-unbinding kinetics of mechanosensitive membrane-bound proteins involved in mechanochemical signaling, such as integrins. Since its introduction and subsequent development as a computational tool, the motor clutch model has been instrumental in elucidating the impact of biophysical factors on cellular mechanobiology. This review aims to provide a comprehensive overview of recent advances in the motor-clutch modeling framework, its role in elucidating the relationships between mechanical forces and cellular processes, and its potential applications in mechanomedicine.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 3","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000305/pdfft?md5=fa0e09270b56f66d1532b26e7001ea1d&pid=1-s2.0-S2949907024000305-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140773794","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":"Advances in micropatterning technology for mechanotransduction research","authors":"Xinyu Hu , Min Bao","doi":"10.1016/j.mbm.2024.100066","DOIUrl":"10.1016/j.mbm.2024.100066","url":null,"abstract":"<div><p>Micropatterning is a sophisticated technique that precisely manipulates the spatial distribution of cell adhesion proteins on various substrates across multiple scales. This precise control over adhesive regions facilitates the manipulation of architectures and physical constraints for single or multiple cells. Furthermore, it allows for an in-depth analysis of how chemical and physical properties influence cellular functionality. In this comprehensive review, we explore the current understanding of the impact of geometrical confinement on cellular functions across various dimensions, emphasizing the benefits of micropatterning in addressing fundamental biological queries. We advocate that utilizing directed self-organization via physical confinement and morphogen gradients on micropatterned surfaces represents an innovative approach to generating functional tissue and controlling morphogenesis in vitro. Integrating this technique with cutting-edge technologies, micropatterning presents a significant potential to bridge a crucial knowledge gap in understanding core biological processes.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 3","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000299/pdfft?md5=0c38744e2d4e1a7de711ec2c0ce1dd83&pid=1-s2.0-S2949907024000299-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140405018","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 roles of extracellular vesicles released by mechanically stimulated osteocytes in regulating osteoblast and osteoclast functions","authors":"Yumei Chen , Runze Zhao , Li Yang , X. Edward Guo","doi":"10.1016/j.mbm.2024.100065","DOIUrl":"10.1016/j.mbm.2024.100065","url":null,"abstract":"<div><p>Bone adapts to mechanical loading by changing its shape and mass. Osteocytes, as major mechanosensors, are critical for bone modeling/remodeling in response to mechanical stimuli. Intracellular calcium oscillation is one of the early responses in osteocytes, and this further facilitates bone cell communication through released biochemical signals. Our previous study has found that mechanically induced calcium oscillations in osteocytes enhance the release of extracellular vesicles (EVs), and those released EVs can elevate bone formation activity. However, the mechanism of mechanically stimulated EVs’ regulation of bone formation and resorption is still unclear. Here, using <em>in vitro</em> studies, we exposed OCY454 cells, with relatively high sclerostin expression, to steady fluid flow (SFF) and characterized the functions of rapidly released EVs in osteoblast and osteoclast regulation. Our study demonstrates that SFF stimulates intracellular calcium response in OCY454 cells and further induces sclerostin, osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL) inside or outside EVs to regulate osteoblast and osteoclast activities. This load-induced protein and EVs release is load-duration dependent. Moreover, stimulated osteocytes rapidly regulate osteoclast maturation through EVs capsulated RANKL. In contrast, other regulating proteins, OPG, and sclerostin, are mainly released directly into the medium without EV capsulation.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000287/pdfft?md5=e2faf11abd74c6b1e6ba230c7caae064&pid=1-s2.0-S2949907024000287-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400797","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":"Force-dependent rapid immunoassay of high specificity and sensitivity","authors":"Xiaodan Zhao , Yanqige Jiang , Yu Zhou , Jie Yan","doi":"10.1016/j.mbm.2024.100061","DOIUrl":"10.1016/j.mbm.2024.100061","url":null,"abstract":"<div><p>The significance of early detection and isolation of infected individuals, along with the quantitative assessment of antibodies against the virus, has gained widespread recognition during the ongoing covid-19 pandemic. This necessitates the development of cost-effective, user-friendly, decentralized testing methods characterized by both high sensitivity and specificity. In this article, we present a comprehensive review of an innovative, low-cost rapid decentralized immunoassay technology, applicable across various diagnostic and quantitative testing scenarios. Distinguishing itself from conventional immunoassay technologies, this method is featured with mechanically enhanced specificity without compromising sensitivity. We delve into the basic principle of the technology and a comparative analysis of this technology in relation to other immunodiagnostic methods, highlighting its potential applications in a wide spectrum of diagnostic tests.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294990702400024X/pdfft?md5=b7ada7bbcba250dbadd8f2c252ecf433&pid=1-s2.0-S294990702400024X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140281138","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":"Probing the protrusions: lamellipodia and filopodia in cancer invasion and beyond","authors":"Laras Pratiwi, Elisa Elisa, Henry Sutanto","doi":"10.1016/j.mbm.2024.100064","DOIUrl":"https://doi.org/10.1016/j.mbm.2024.100064","url":null,"abstract":"<div><p>The dynamic protrusions of lamellipodia and filopodia have emerged as crucial players in tumor progression and metastasis. These membrane structures, governed by intricate actin cytoskeletal rearrangements, facilitate cancer cell migration, invasion, and interaction with the tumor microenvironment. This review provides a comprehensive examination of the structural and functional attributes of lamellipodia and filopodia, shedding light on their pivotal roles in mediating cancer invasion. Navigating through the intricate landscape of cancer biology, the review illuminates the intricate signaling pathways and regulatory mechanisms orchestrating the formation and activity of these protrusions. The discussion extends to the clinical implications of lamellipodia and filopodia, exploring their potential as diagnostic and prognostic markers, and delving into therapeutic strategies that target these structures to impede cancer progression. As we delve into the future, the review outlines emerging technologies and unexplored facets that beckon further research, emphasizing the need for collaborative efforts to unravel the complexities of lamellipodia and filopodia in cancer, ultimately paving the way for innovative therapeutic interventions.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000275/pdfft?md5=5e8e0610146b04739a39d45afef98e3d&pid=1-s2.0-S2949907024000275-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140209064","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}
Kaide Xia , Wenhui Hu , Yun Wang , Jin Chen , Zuquan Hu , Chenyi An , Pu Xu , Lijing Teng , Jieheng Wu , Lina Liu , Sichao Zhang , Jinhua Long , Zhu Zeng
{"title":"Extracellular matrix stiffness modulates the mechanophenotypes and focal adhesions of colon cancer cells leading to their invasions via YAP1","authors":"Kaide Xia , Wenhui Hu , Yun Wang , Jin Chen , Zuquan Hu , Chenyi An , Pu Xu , Lijing Teng , Jieheng Wu , Lina Liu , Sichao Zhang , Jinhua Long , Zhu Zeng","doi":"10.1016/j.mbm.2024.100062","DOIUrl":"10.1016/j.mbm.2024.100062","url":null,"abstract":"<div><p>Distal metastasis is the main cause of clinical treatment failure in patients with colon cancer. It is now known that the invasion and metastasis of cancer cells is precisely regulated by chemical and physical factors <em>in vivo</em>. However, the role of extracellular matrix (ECM) stiffness in colon cancer cell (CCCs) invasion and metastasis remains unclear. Here, bioinformatical analysis suggested that a high expression level of yes associated protein 1 (YAP1) was significantly associated with metastasis and poor prognosis in colon cancer patients. We further investigated the effects of polyacrylamide hydrogels with different stiffnesses (3, 20, and 38 kPa), which were simulated as ECM, on the mechanophenotype (F-actin cytoskeleton organization, electrophoretic rate, membrane fluidity, and Young's modulus) of CCCs. The results showed that a stiffer ECM could induce the maturation of focal adhesions and formation of stress fibers in CCCs, regulate their mechanophenotypes, and promote cell motility. We also demonstrated that the expression levels of YAP1 and paxillin were positively correlated in patients with colon cancer. YAP1 knockdown reduces paxillin clustering and cell motility and alters the cellular mechanophenotypes of CCCs. This is of great significance for an in-depth understanding of the invasion and metastatic mechanisms of colon cancer and for the optimization of clinical therapy from the perspective of mechanobiology.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000251/pdfft?md5=8225712552eb8e5633ae7b59efe64ce1&pid=1-s2.0-S2949907024000251-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140280551","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}