Mechanobiology in Medicine最新文献

{"title":"Low-magnitude high-frequency vibration reduces prostate cancer growth and extravasation in vitro","authors":"Amel Sassi ,&nbsp;Kimberly Seaman ,&nbsp;Xin Song ,&nbsp;Chun-Yu Lin ,&nbsp;Yu Sun ,&nbsp;Lidan You","doi":"10.1016/j.mbm.2024.100095","DOIUrl":"10.1016/j.mbm.2024.100095","url":null,"abstract":"<div><p>Prostate cancer (PCa) continues to rank among the most common malignancies in Europe and North America with significant mortality rates despite advancements in detection and treatment. Physical activity is often recommended to PCa patients due to its benefits in preventing disease recurrence and managing treatment-related side effects. However, physical activity may be challenging for elderly or bedridden patients. As such, vibration therapy has been proposed as a safe, effective, and easy to perform alternative treatment that may confer similar effects as physical exercise. Specifically, low-magnitude high frequency (LMHF) vibration has been shown to decrease breast cancer extravasation into the bone and reduce other types of cancer proliferation by impacting cell viability. Here, we investigated the effects of daily application of LMHF vibration (0.3 ​g, 60 ​Hz, 1 ​hour/day for 3 days) on prostate cancer growth and bone metastasis <em>in vitro</em>. Our findings suggest that LMHF vibration significantly reduces colony formation through a decrease in cell growth and proliferation. Moreover, using a 3D cell culture model, LMHF vibration significantly reduces PC3 spheroid size. Additionally, LMHF vibration reduces PCa cell extravasation into the bone microenvironment through the stimulation of osteocytes and subsequent osteocyte-endothelial cell cross talk. These findings highlight the potential of LMHF vibration for managing PCa growth and metastasis.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000585/pdfft?md5=948df38812a9b1c7c90cfc8e5ef3d321&pid=1-s2.0-S2949907024000585-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142129716","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":"Application of biomechanics in tumor epigenetic research","authors":"Qi Wang ,&nbsp;Xiaohong Yin ,&nbsp;Yunyi Ding ,&nbsp;Hong Zhao ,&nbsp;Yichen Luo","doi":"10.1016/j.mbm.2024.100093","DOIUrl":"10.1016/j.mbm.2024.100093","url":null,"abstract":"<div><p>The field of cancer research is increasingly recognizing the complex interplay between biomechanics and tumor epigenetics. Biomechanics plays a significant role in the occurrence, development, and metastasis of cancer and may exert influence by impacting the epigenetic modifications of tumors. In this review, we investigate a spectrum of biomechanical tools, including computational models, measurement instruments, and in vitro simulations. These tools not only assist in deciphering the mechanisms behind these epigenetic changes but also provide novel methods for characterizing tumors, which are significant for diagnosis and treatment. Finally, we discuss the potential of new therapies that target the biomechanical properties of the tumor microenvironment. There is hope that by altering factors such as the stiffness of the extracellular matrix or interfering with mechano-sensing pathways, we can halt tumor progression through epigenetic mechanisms. We emphasize the necessity for multidisciplinary efforts to integrate biomechanics with tumor epigenetics more comprehensively. Such collaboration is anticipated to advance therapeutic strategies and enhance our understanding of cancer biology, signaling the dawn of a new era in cancer treatment and research.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000561/pdfft?md5=2b0b12971d7ff6eb0193e7d386c7f22d&pid=1-s2.0-S2949907024000561-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098530","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":"YAP/TAZ as mechanobiological signaling pathway in cardiovascular physiological regulation and pathogenesis","authors":"Rakibul Islam,&nbsp;Zhongkui Hong","doi":"10.1016/j.mbm.2024.100085","DOIUrl":"10.1016/j.mbm.2024.100085","url":null,"abstract":"<div><p>Cardiovascular diseases (CVDs) persistently rank as a leading cause of premature death and illness worldwide. The Hippo signaling pathway, known for its highly conserved nature and integral role in regulating organ size, tissue homeostasis, and stem cell function, has been identified as a critical factor in the pathogenesis of CVDs. Recent findings underscore the significance of the Yes-associated protein (YAP) and the Transcriptional Coactivator with PDZ-binding motif (TAZ), collectively referred to as YAP/TAZ. These proteins play pivotal roles as downstream components of the Hippo pathway, in the regulation of cardiovascular development and homeostasis. YAP/TAZ can regulate various cellular processes such as cell proliferation, migration, differentiation, and apoptosis through their interactions with transcription factors, particularly those within the transcriptional enhancer associate domain (TEAD) family. The aim of this review is to provide a comprehensive overview of the current understanding of YAP/TAZ signaling in cardiovascular physiology and pathogenesis. We analyze the regulatory mechanisms of YAP/TAZ activation, explore their downstream effectors, and examine their association across numerous cardiovascular disorders, including myocardial hypertrophy, myocardial infarction, pulmonary hypertension, myocardial ischemia-reperfusion injury, atherosclerosis, angiogenesis, restenosis, and cardiac fibrosis. Furthermore, we investigate the potential therapeutic implications of targeting the YAP/TAZ pathway for the treatment of CVDs. Through this comprehensive review, our aim is to elucidate the current understanding of YAP/TAZ signaling in cardiovascular biology and underscore its potential implications for the diagnosis and therapeutic intervention of CVDs.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000482/pdfft?md5=452c635adfe6740a9f2f78624f8b36f6&pid=1-s2.0-S2949907024000482-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141985246","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":"Viscoelasticity of ECM and cells—origin, measurement and correlation","authors":"Zhiqiang Liu,&nbsp;Si Da Ling,&nbsp;Kaini Liang,&nbsp;Yihan Chen,&nbsp;Yudi Niu,&nbsp;Lei Sun,&nbsp;Junyang Li,&nbsp;Yanan Du","doi":"10.1016/j.mbm.2024.100082","DOIUrl":"10.1016/j.mbm.2024.100082","url":null,"abstract":"<div><p>The extracellular matrix (ECM) and cells are crucial components of natural tissue microenvironments, and they both demonstrate dynamic mechanical properties, particularly viscoelastic behaviors, when exposed to external stress or strain over time. The capacity to modify the mechanical properties of cells and ECM is crucial for gaining insight into the development, physiology, and pathophysiology of living organisms. As an illustration, researchers have developed hydrogels with diverse compositions to mimic the properties of the native ECM and use them as substrates for cell culture. The behavior of cultured cells can be regulated by modifying the viscoelasticity of hydrogels. Moreover, there is widespread interest across disciplines in accurately measuring the mechanical properties of cells and the surrounding ECM, as well as exploring the interactive relationship between these components. Nevertheless, the lack of standardized experimental methods, conditions, and other variables has hindered systematic comparisons and summaries of research findings on ECM and cell viscoelasticity. In this review, we delve into the origins of ECM and cell viscoelasticity, examine recently developed methods for measuring ECM and cell viscoelasticity, and summarize the potential interactions between cell and ECM viscoelasticity. Recent research has shown that both ECM and cell viscoelasticity experience alterations during in vivo pathogenesis, indicating the potential use of tailored viscoelastic ECM and cells in regenerative medicine.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000457/pdfft?md5=d6a24f3aa25c8acf54e6bcfd62d47df9&pid=1-s2.0-S2949907024000457-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058276","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":"A microbiome-dependent gut-bone axis determines skeletal benefits from mechanical loading","authors":"X. Edward Guo","doi":"10.1016/j.mbm.2024.100084","DOIUrl":"10.1016/j.mbm.2024.100084","url":null,"abstract":"<div><p>A recent study published in <em>Cell Metabolism</em> entitled “Gut microbial alterations in arginine metabolism determine bone mechanical adaptation” demonstrated that administration of L-arginine enhanced bone mechanical adaptation by activating a nitric oxide-calcium feedback loop in osteocytes. The findings revealed that mechanical regulation of bone adaptation is associated with gut microbiota. The underlying cause of heterogeneity of bone mechanoresponsiveness was the significant difference in the composition of the gut microbiota, in which the family <em>Lachnospiraceae</em> contributed to the inter-individual high variability in bone mechanical adaptation. Additionally, administration of <em>Lachnospiraceae</em> exhibited increased expression levels of L-citrulline and L-arginine and enhanced bone mechanoresponsiveness in recipients. Collectively, this study provides mechanistic insights into inter-individual variability of the gut microbial, which is related to the heterogeneity of bone mechanical adaptation and provides a novel preventive and therapeutic strategy to anti-osteoporotic for maximizing bone mechanoresponsiveness via the microbiota-metabolite axis.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 3","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000470/pdfft?md5=01576b678e93cfb75c71a174b559d30e&pid=1-s2.0-S2949907024000470-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851738","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":"From sequence to mechanobiology? Promises and challenges for AlphaFold 3","authors":"Francesco Zonta ,&nbsp;Sergio Pantano","doi":"10.1016/j.mbm.2024.100083","DOIUrl":"10.1016/j.mbm.2024.100083","url":null,"abstract":"<div><p>Interactions between macromolecules orchestrate many mechanobiology processes. However, progress in the field has often been hindered by the monetary and time costs of obtaining reliable experimental structures. In recent years, deep-learning methods, such as AlphaFold, have democratized access to high-quality predictions of the structural properties of proteins and other macromolecules. The newest implementation, AlphaFold 3, significantly expands the applications of its predecessor, AlphaFold 2, by incorporating reliable models for small molecules and nucleic acids and enhancing the prediction of macromolecular complexes. While several limitations still exist, the continuous improvement of machine learning methods like AlphaFold is producing a significant revolution in the field. The possibility of easily accessing structural predictions of biomolecular complexes may create substantial impacts in mechanobiology. Indeed, structural studies are at the basis of several applications in the field, such as drug discovery for mechanosensing proteins, development of mechanotherapy, understanding the mechanotransduction mechanisms and the mechanistic basis of diseases, or designing biomaterials for tissue engineering.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 3","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000469/pdfft?md5=e9e8d648eaef2a1a12526a3a9cbe4a52&pid=1-s2.0-S2949907024000469-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842240","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":"Effects of gravity, microgravity or microgravity simulation on early mouse embryogenesis: A review of the first two space embryo studies","authors":"Douglas M. Ruden ,&nbsp;Daniel A. Rappolee","doi":"10.1016/j.mbm.2024.100081","DOIUrl":"10.1016/j.mbm.2024.100081","url":null,"abstract":"<div><p>Many simulated micro-gravity (micro-G) experiments on earth suggest that micro-G conditions are not compatible with early mammalian embryo development. Recently, the first two “space embryo” studies have been published showing that early mouse embryo development can occur in real microgravity (real micro-G) conditions in orbit. In the first of these studies, published in 2020, Lei and collaborators developed automated mini-incubator (AMI) devices for mouse embryos facilitating cultivation, microscopic observation, and fixation¹. Within these AMI apparatuses, 3400 non-frozen 2-cell embryos were launched in a recoverable satellite, experiencing sustained microgravity (∼0.001G) for 64 ​h post-orbit before fixation in space and recovery on earth. In a subsequent study, in 2023, Wakayama and colleagues² devised Embryo Thawing and Culturing (ETC) devices, enabling manual thawing, cultivation, and fixation of frozen 2-cell mouse embryos by a trained astronaut aboard the International Space Station (ISS). Within the ETCs, a total of 720 2-cell mouse embryos underwent thawing and cultivation for 4 days on the ISS, subject to either microgravity (n ​= ​360) and simulated-1G (n ​= ​360) conditions. The primary findings from both space embryo experiments indicate that mouse embryos can progress through embryogenesis from the 2-cell stage to the blastocyst stage under real micro-G conditions with few defects. Collectively, these studies propose the potential for mammalian reproduction under real micro-G conditions, challenging earlier simulated micro-G research suggesting otherwise.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000445/pdfft?md5=7fac1cfeb0aa7e577b2502ddcad5ca49&pid=1-s2.0-S2949907024000445-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732205","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":"Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields","authors":"M. Ete Chan ,&nbsp;Christopher Ashdown ,&nbsp;Lia Strait ,&nbsp;Sishir Pasumarthy ,&nbsp;Abdullah Hassan ,&nbsp;Steven Crimarco ,&nbsp;Chanpreet Singh ,&nbsp;Vihitaben S. Patel ,&nbsp;Gabriel Pagnotti ,&nbsp;Omor Khan ,&nbsp;Gunes Uzer ,&nbsp;Clinton T. Rubin","doi":"10.1016/j.mbm.2024.100080","DOIUrl":"10.1016/j.mbm.2024.100080","url":null,"abstract":"<div><p>Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using <em>biological</em> or <em>chemical</em> strategies, harnessing cell mechanosensitivity represents a promising – albeit less studied – <em>physical</em> pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; &lt;1 ​g, 10–500 ​Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in Chinese Hamster Ovary (CHO)-adherent cells (+79% in 96 ​hr) using a particular set of LIV parameters (0.2 ​g, 500 ​Hz, 3 ​× ​30 ​min/d, 2 ​hr refractory period), yet this same mechanical input <em>suppressed</em> proliferation in CHO-suspension cells (−13%). Another set of LIV parameters (30 ​Hz, 0.7 ​g, 2 ​× ​60 ​min/d, 2 ​hr refractory period) however, were able to increase the proliferation of CHO-suspension cells by 210% and T-cells by 20.3%. Importantly, we also reported that T-cell response to LIV was in-part dependent upon AKT phosphorylation, as inhibiting AKT phosphorylation reduced the proliferative effect of LIV by over 60%, suggesting that suspension cells utilize mechanism(s) similar to adherent cells to sense specific LIV signals. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (&gt;90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, it's highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000433/pdfft?md5=018ef78186c038e68b40852d4fefb32a&pid=1-s2.0-S2949907024000433-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736469","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":"Mechanobiomaterials: Harnessing mechanobiology principles for tissue repair and regeneration","authors":"Xiao Lin ,&nbsp;Hua Yang ,&nbsp;Yi Xia ,&nbsp;Kang Wu ,&nbsp;Fengcheng Chu ,&nbsp;Huan Zhou ,&nbsp;Huajian Gao ,&nbsp;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":"2 3","pages":"Article 100079"},"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}

{"title":"Mechanical force induced activation of adhesion G protein–coupled receptor","authors":"Yueming Xu ,&nbsp;Huanhuan Xu ,&nbsp;Jie Yan ,&nbsp;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":"2 3","pages":"Article 100078"},"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}