Pub Date : 2024-05-16DOI: 10.1016/j.mbm.2024.100079
Xiao Lin , Hua Yang , Yi Xia , Kang Wu , Fengcheng Chu , Huan Zhou , Huajian Gao , Lei Yang
Mechanical stimuli are known to play critical roles in mediating tissue repair and regeneration. Recently, this knowledge has led to a paradigm shift toward proactive programming of biological functionalities of biomaterials by leveraging mechanics–geometry–biofunction relationships, which are beginning to shape the newly emerging field of mechanobiomaterials. To profile this emerging field, this article aims to elucidate the fundamental principles in modulating biological responses with material–tissue mechanical interactions, illustrate recent findings on the relationships between material properties and biological responses, discuss the importance of mathematical/physical models and numerical simulations in optimizing material properties and geometry, and outline design strategies for mechanobiomaterials and their potential for tissue repair and regeneration. Given that the field of mechanobiomaterials is still in its infancy, this article also discusses open questions and challenges that need to be addressed.
{"title":"Mechanobiomaterials: Harnessing mechanobiology principles for tissue repair and regeneration","authors":"Xiao Lin , Hua Yang , Yi Xia , Kang Wu , Fengcheng Chu , Huan Zhou , Huajian Gao , Lei Yang","doi":"10.1016/j.mbm.2024.100079","DOIUrl":"10.1016/j.mbm.2024.100079","url":null,"abstract":"<div><p>Mechanical stimuli are known to play critical roles in mediating tissue repair and regeneration. Recently, this knowledge has led to a paradigm shift toward proactive programming of biological functionalities of biomaterials by leveraging mechanics–geometry–biofunction relationships, which are beginning to shape the newly emerging field of mechanobiomaterials. To profile this emerging field, this article aims to elucidate the fundamental principles in modulating biological responses with material–tissue mechanical interactions, illustrate recent findings on the relationships between material properties and biological responses, discuss the importance of mathematical/physical models and numerical simulations in optimizing material properties and geometry, and outline design strategies for mechanobiomaterials and their potential for tissue repair and regeneration. Given that the field of mechanobiomaterials is still in its infancy, this article also discusses open questions and challenges that need to be addressed.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000421/pdfft?md5=320fe996100a6e4b52edd7711af259b4&pid=1-s2.0-S2949907024000421-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041150","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}
Pub Date : 2024-05-14DOI: 10.1016/j.mbm.2024.100078
Yueming Xu , Huanhuan Xu , Jie Yan , Gaojie Song
Among the various families of G protein-couple receptors (GPCR), the adhesion family of GPCRs is specialized by its expansive extracellular region, which facilitates the recruitment of various ligands. Previous hypothesis proposed that aGPCRs are activated by mechanical force, wherein a Stachel peptide is liberated from the GPCR autoproteolysis-inducing (GAIN) domain and subsequently binds to the transmembrane domain (7TM) upon activation. In this review, we summarize recent advancements in structural studies of aGPCRs, unveiling a conserved structural change of the Stachel peptide from the GAIN domain-embedded β-strand conformation to the 7TM-loaded α-helical conformation. Notably, using single-molecule studies, we directly observed the unfolding of GAIN domain and the release of Stachel peptide under physiological level of force, precisely supporting the mechanosensing mechanism for aGPCRs. We observed that the current complex structures of aGPCR adhesion domains with their respective ligands share a common pattern with the C-termini of each binding partner extending in opposite directions, suggesting a similar shearing stretch geometry for these aGPCRs to transmit the mechanical force generated in the circulating environment to the GAIN domain for its unfolding. Outstanding questions, including the relative orientations and interactions between 7TM and its preceding GAIN and adhesion domains of different aGPCRs, may require further structural and mechanical studies at the full-length receptor scale or cell-based level. Our analysis extends the current view of aGPCR structural organization and activation and offers valuable insights for the development of mechanosensor based on aGPCRs or discovery of mechanotherapy against aGPCRs.
在各种 G 蛋白偶联受体(GPCR)家族中,粘附 GPCR 家族因其扩张的胞外区域而具有特殊性,这有利于各种配体的招募。以前的假说认为,aGPCR 是由机械力激活的,激活时,Stachel 肽从 GPCR 自体蛋白水解诱导(GAIN)结构域中释放出来,随后与跨膜结构域(7TM)结合。在这篇综述中,我们总结了 aGPCR 结构研究的最新进展,揭示了 Stachel 肽从 GAIN 结构域嵌入的 β 链构象到 7TM 加载的 α 螺旋构象的保守结构变化。值得注意的是,通过单分子研究,我们直接观察到了 GAIN 结构域在生理作用力下的展开和 Stachel 肽的释放,这恰恰支持了 aGPCR 的机械传感机制。我们观察到,目前 aGPCR 粘附结构域与各自配体的复合物结构有一个共同的模式,即每个结合伙伴的 C 端向相反的方向延伸,这表明这些 aGPCR 具有类似的剪切拉伸几何结构,可将循环环境中产生的机械力传递给 GAIN 结构域,使其展开折叠。悬而未决的问题,包括不同 aGPCR 的 7TM 与其前面的 GAIN 和粘附结构域之间的相对方向和相互作用,可能需要在全长受体尺度或细胞水平上进行进一步的结构和机械研究。我们的分析扩展了目前对 aGPCR 结构组织和激活的看法,并为开发基于 aGPCR 的机械传感器或发现针对 aGPCR 的机械疗法提供了宝贵的见解。
{"title":"Mechanical force induced activation of adhesion G protein–coupled receptor","authors":"Yueming Xu , Huanhuan Xu , Jie Yan , Gaojie Song","doi":"10.1016/j.mbm.2024.100078","DOIUrl":"10.1016/j.mbm.2024.100078","url":null,"abstract":"<div><p>Among the various families of G protein-couple receptors (GPCR), the adhesion family of GPCRs is specialized by its expansive extracellular region, which facilitates the recruitment of various ligands. Previous hypothesis proposed that aGPCRs are activated by mechanical force, wherein a <em>Stachel</em> peptide is liberated from the GPCR autoproteolysis-inducing (GAIN) domain and subsequently binds to the transmembrane domain (7TM) upon activation. In this review, we summarize recent advancements in structural studies of aGPCRs, unveiling a conserved structural change of the <em>Stachel</em> peptide from the GAIN domain-embedded β-strand conformation to the 7TM-loaded α-helical conformation. Notably, using single-molecule studies, we directly observed the unfolding of GAIN domain and the release of <em>Stachel</em> peptide under physiological level of force, precisely supporting the mechanosensing mechanism for aGPCRs. We observed that the current complex structures of aGPCR adhesion domains with their respective ligands share a common pattern with the C-termini of each binding partner extending in opposite directions, suggesting a similar shearing stretch geometry for these aGPCRs to transmit the mechanical force generated in the circulating environment to the GAIN domain for its unfolding. Outstanding questions, including the relative orientations and interactions between 7TM and its preceding GAIN and adhesion domains of different aGPCRs, may require further structural and mechanical studies at the full-length receptor scale or cell-based level. Our analysis extends the current view of aGPCR structural organization and activation and offers valuable insights for the development of mechanosensor based on aGPCRs or discovery of mechanotherapy against aGPCRs.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294990702400041X/pdfft?md5=bf52735e6165c1ef20cbbeb3f0ccd37a&pid=1-s2.0-S294990702400041X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141035304","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}
Pub Date : 2024-05-03DOI: 10.1016/j.mbm.2024.100071
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
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-04-29DOI: 10.1016/j.mbm.2024.100069
Si-Yu Hu , Chun-Dong Xue , Yong-Jiang Li , Shen Li , Zheng-Nan Gao , Kai-Rong Qin
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 (Ca2+) 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 in vitro 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 in vitro. 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 Ca2+ 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.
糖耐量异常会导致动脉内皮损伤,这是糖尿病患者血管并发症的早期关键事件。在生理学上,适度的剪切应力(SS)有助于维持内皮细胞的健康和正常功能。活性氧(ROS)和钙离子(Ca2+)信号参与了血糖异常引起的内皮功能障碍,也与 SS 介导的内皮细胞功能调节有关。因此,当务之急是建立研究内皮生物力学和机械生物学的体外模型,以寻求利用适当的 SS 来延缓或逆转内皮功能障碍的干预措施。微流控技术作为一种新方法,可以在体外复制血糖环境和准确的脉冲式 SS。在此,我们回顾了微流控系统用于 SS 介导的血糖异常诱导的内皮细胞损伤(ECD)修复的进展,揭示了 ROS 和 Ca2+ 在这一过程中的关键作用。这对寻找适当的机械干预方法(如运动训练)以预防和治疗糖尿病心血管并发症具有重要意义。
{"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":null,"pages":null},"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}
Pub Date : 2024-04-27DOI: 10.1016/j.mbm.2024.100070
Wenqiang Du , Ashkan Novin , Yamin Liu , Junaid Afzal , Shaofei Liu , Yasir Suhail , Kshitiz
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-04-27DOI: 10.1016/j.mbm.2024.100068
Brian Chesney Quartey , Gabriella Torres , Mei ElGindi , Aseel Alatoom , Jiranuwat Sapudom , Jeremy CM Teo
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-04-03DOI: 10.1016/j.mbm.2024.100067
Zhao Xu , Feng Xu , Bo Cheng
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-03-28DOI: 10.1016/j.mbm.2024.100066
Xinyu Hu , Min Bao
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-03-27DOI: 10.1016/j.mbm.2024.100065
Yumei Chen , Runze Zhao , Li Yang , X. Edward Guo
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 in vitro 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.
骨骼通过改变其形状和质量来适应机械负荷。骨细胞作为主要的机械传感器,对骨建模/重塑以应对机械刺激至关重要。细胞内钙振荡是骨细胞的早期反应之一,它通过释放生化信号进一步促进骨细胞的交流。我们之前的研究发现,机械刺激引起的成骨细胞钙振荡会促进细胞外囊泡(EVs)的释放,而这些释放的EVs可提高骨形成活性。然而,机械刺激EVs调节骨形成和吸收的机制仍不清楚。在此,我们利用体外研究,将硬骨素表达相对较高的 OCY454 细胞暴露于稳定液流(SFF)中,并描述了快速释放的 EVs 在成骨细胞和破骨细胞调控中的功能。我们的研究表明,SFF能刺激OCY454细胞的细胞内钙反应,并进一步诱导EVs内外的硬骨素、骨保护素(OPG)、NF-κB配体受体激活剂(RANKL)调节成骨细胞和破骨细胞的活性。这种负荷诱导的蛋白质和 EVs 释放与负荷持续时间有关。此外,受刺激的成骨细胞通过EVs包裹的RANKL迅速调节破骨细胞的成熟。相比之下,其他调节蛋白、OPG 和硬骨生成素主要是直接释放到培养基中,而没有被 EV 包囊。
{"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":null,"pages":null},"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}
Pub Date : 2024-03-21DOI: 10.1016/j.mbm.2024.100061
Xiaodan Zhao , Yanqige Jiang , Yu Zhou , Jie Yan
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.
{"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":null,"pages":null},"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}