Mechanobiology in Medicine最新文献

{"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":"2024-12-01","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":"Strain and hyaluronic acid interact to regulate ovarian cancer cell proliferation, migration, and drug resistance","authors":"Maranda Kramer ,&nbsp;Allyson Criswell ,&nbsp;Kamari Marzette ,&nbsp;Emerson Cutcliffe ,&nbsp;Mary Kathryn Sewell-Loftin","doi":"10.1016/j.mbm.2024.100094","DOIUrl":"10.1016/j.mbm.2024.100094","url":null,"abstract":"<div><p>The ovarian tumor microenvironment plays a critical yet is poorly understood role in the regulation of cancer cell behaviors including proliferation, migration, and response to chemotherapy treatments. Ovarian cancer is the deadliest gynecological cancer, due to diagnosis at late stages of the disease and increased resistance to chemotherapies for recurrent disease. Understanding how the tumor microenvironment (TME) interacts with biomechanical forces to drive changes to ovarian cancer cell behaviors could elucidate novel treatment strategies for this patient population. Additionally, limitations in current preclinical models of the ovarian TME do not permit investigation of crosstalk between signaling pathways and mechanical forces. Our study focused on uncovering how strains and hyaluronic acid (HA) interact to signal through the CD44 receptor to alter ovarian cancer cell growth, migration, and response to a commonly used chemotherapy, paclitaxel. Using an advanced 3D <em>in vitro</em> model, we were able to identify how interactions of strain and HA as in the TME synergistically drive enhanced proliferation and migration in an ovarian tumor model line, while decreasing response to paclitaxel treatment. This study demonstrates the importance of elucidating how the mechanical forces present in the ovarian TME drive disease progression and response to treatment.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000573/pdfft?md5=bf83a1132a805e7989290d565149d346&pid=1-s2.0-S2949907024000573-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122418","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":"Harnessing mechanobiology to enhance cell therapy","authors":"Peixiang Ma ,&nbsp;An Qin ,&nbsp;Tobias Winkler ,&nbsp;Jie Zhao","doi":"10.1016/j.mbm.2024.100102","DOIUrl":"10.1016/j.mbm.2024.100102","url":null,"abstract":"<div><div>Recent developments in cell therapy have revolutionized medical treatment. While various methods of stimulation have been explored, the role of mechanical force has often been overlooked. Although mechanical loading is not easily visible, it can actively reshape organisms, and abnormal mechanical loading can lead to injury and disease. By leveraging the mechanobiology of cells, we can equip them with synthetic mechanosensors that can redirect genetic circuits to express protective factors, such as antibodies and cytokines, according to the mechanical force signal. The advancement of artificial intelligence (AI) presents a fascinating opportunity to redesign more complex mechanoreceptors, allowing cells to respond to intricate stimuli. Additionally, genetic engineering tools like CRISPR-Cas9, base editing, and prime editing enable the creation of multiple gene circuits for cells to react to complex mechanical environments. Advanced mechanical loading techniques, such as focused ultrasound, deliver signals in a confined spatial and temporal manner. Therefore, harnessing mechanobiology in cells can develop more flexible, personalized, and precise cell therapies.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142723640","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":"2024-12-01","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":"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":"2024-12-01","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":"miRNA in mechanobiology: The exploration needs to continue","authors":"Kai Huang,&nbsp;Yingxin Qi","doi":"10.1016/j.mbm.2024.100101","DOIUrl":"10.1016/j.mbm.2024.100101","url":null,"abstract":"<div><div>The 2024 Nobel Prize in Physiology or Medicine has once again sparked considerable interest in microRNA (miRNA). Recent advances have unveiled that miRNAs play critical roles in mediating the effects of mechanical stimuli on gene expression, cellular functions, tissue development, and disease progression. This perspective summarized the history of miRNA research and highlighted the promising research directions of miRNAs in the field of mechanobiology.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100101"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703966","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":"2024-12-01","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":"2024-12-01","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":"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":"2024-09-01","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":"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":"2024-09-01","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}