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}
{"title":"Bead-based microfluidic platforms for multiplex and ultrasensitive immunoassays in clinical diagnosis and treatment","authors":"Xiaoxia Fang, Yiwen Yang, Heni Wang, Hong Xu","doi":"10.1016/j.mbm.2024.100063","DOIUrl":"10.1016/j.mbm.2024.100063","url":null,"abstract":"<div><p>Multiplex ultrasensitive detection of low abundance proteins remains a significant challenge in clinical applications, necessitating the development of innovative solutions. The integration of bead-based microfluidic chip platforms with their efficient target capture and separation capabilities, along with the advantages of miniaturization and low reagent consumption, holds great promise for building an integrated point-of-care testing (POCT) system that enables seamless sample input-result output. This review presents a comprehensive overview of recent advancements in bead-based microfluidic platforms for multiplex and ultrasensitive immunoassays, along with their potential applications in clinical diagnosis and treatment, which is organized into four sections: encoding techniques, the role of microfluidic platforms, applications, and future prospects.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000263/pdfft?md5=6e5a8a8197a33fba655951a040622044&pid=1-s2.0-S2949907024000263-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140268622","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":"Regulatory role of interfacial adhesion and mechanical microenvironments in microbe-host interactions","authors":"Yuting Feng, Jianyong Huang","doi":"10.1016/j.mbm.2024.100060","DOIUrl":"10.1016/j.mbm.2024.100060","url":null,"abstract":"<div><p>A recent study published in <em>Nature Communications</em> showed that essential modulatory roles of interfacial adhesion and mechanical microenvironments such as geometric constraints and extracellular matrix stiffness, in microbe-host cell interactions. This study utilized single-cell force spectroscopy and RNA sequencing to gain insight into the intrinsic mechanisms by which the mechanical microenvironment regulates bacterial-host interactions and therefore reveal potential interventions against bacterial invasion. Meanwhile, the adhesion forces involved in the bacterial–host interactions were recognized as a new indicator for assessing the extent of bacterial infection. Taken together, these findings demonstrate that interfacial adhesion forces and mechanical microenvironments play a dominant role in modulating functions and behaviors of microorganisms and host cells, which also provide a mechanobiology-inspired idea for the development of subsequent drug-resistant antimicrobials and broad-spectrum antiviral drugs.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000238/pdfft?md5=5a9dc4292dc1bffe61407088d51445eb&pid=1-s2.0-S2949907024000238-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140084375","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":"Rescuing SERCA2 pump deficiency: A novel approach to improve bone mechano-responsiveness in type 2 diabetes","authors":"Zhifeng Yu , X. Edward Guo","doi":"10.1016/j.mbm.2024.100047","DOIUrl":"https://doi.org/10.1016/j.mbm.2024.100047","url":null,"abstract":"<div><p>A recent study published in <em>Nature Communications</em> demonstrated that restoring SERCA2 pump deficiency can enhance bone mechano-responsiveness in type 2 diabetes (T2D) by modulating osteocyte calcium dynamics. The findings revealed that in T2D mice, the ability of the bone to respond to mechanical stress is compromised, primarily due to attenuated calcium oscillatory dynamics within osteocytes rather than in osteoblasts or osteoclasts. The underlying mechanism of this reduction in bone mechano-responsiveness in T2D was identified as a specific decrease in osteocytic SERCA2 expression mediated by PPARα. Additionally, mice overexpressing SERCA2 in osteocytes exhibited reduced deterioration of bone mechano-responsiveness induced by T2D. Collectively, this study provides mechanistic insights into T2D-induced deterioration in bone mechano-responsiveness and identifies a promising therapeutic approach to counteract T2D-associated fragility fractures.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100047"},"PeriodicalIF":0.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294990702400010X/pdfft?md5=673fabd07f7fc63f32f1485c817369bc&pid=1-s2.0-S294990702400010X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112983","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 effects of matrix stiffness on immune cells in bone biology","authors":"Ting Jiang , Meng-Ting Zheng , Ruo-Mei Li , Ning-Juan Ouyang","doi":"10.1016/j.mbm.2024.100046","DOIUrl":"10.1016/j.mbm.2024.100046","url":null,"abstract":"<div><p>Bone and immune cells typically inhabit the same microenvironment and engage in mutual interactions to collectively execute the functions of the “osteoimmune system.” Establishing a harmonized and enduring osteoimmune system significantly enhances bone regeneration, necessitating the maintenance of bone and immune homeostasis. Recently, mechanobiology has garnered increasing interest in bone tissue engineering, with matrix stiffness emerging as a crucial parameter that has been extensively investigated. The effect of matrix stiffness on bone homeostasis remains relatively clear. Soft substrates tend to significantly affect the chondrogenic differentiation of bone marrow mesenchymal stem cells, whereas increasing matrix stiffness is advantageous for osteogenic differentiation. Increased stiffness increases osteoclast differentiation and activity. Additionally, there is increasing emphasis on immune homeostasis, which necessitates dynamic communication between immune cells. Immune cells are crucial in initiating bone regeneration and driving early inflammatory responses. Functional changes induced by matrix stiffness are pivotal for determining the outcomes of engineered tissue mimics. However, inconsistent and incomparable findings regarding the responses of different immune cells to matrix stiffness can be perplexing owing to variations in the stiffness range, measurement methods, and other factors. Therefore, this study aimed to provide a comprehensive review of the specific effects of matrix stiffness on diverse immune cells, with a particular focus on its implications for bone regeneration, which would offer theoretical insights into the treatment of large segmental bony defects and assist in the clinical development of new engineering strategies.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000093/pdfft?md5=32830fd5ccb0440aa455483d1f52a402&pid=1-s2.0-S2949907024000093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140465958","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}
Tom M.J. Evers , Joep Beumer , Hans Clevers , Alireza Mashaghi
{"title":"Mechanics of serotonin-producing human entero-endocrine cells","authors":"Tom M.J. Evers , Joep Beumer , Hans Clevers , Alireza Mashaghi","doi":"10.1016/j.mbm.2024.100044","DOIUrl":"10.1016/j.mbm.2024.100044","url":null,"abstract":"<div><p>The gastrointestinal (GI) tract's primary role is food digestion, relying on coordinated fluid secretion and bowel movements triggered by mechanosensation. Enteroendocrine cells (EECs) are specialized mechanosensitive cells that convert mechanical forces into electrochemical signals, culminating in serotonin release to regulate GI motility. Despite their pivotal role, knowledge of EEC mechanical properties has been lacking due to their rarity and limited accessibility. In this brief report, we present the first single-cell mechanical characterization of human ECCs isolated from healthy intestinal organoids. Using single-cell optical tweezers, we measured EEC stiffness profiles at the physiological temperature and investigated changes following tryptophan metabolism inhibition. Our findings not only shed light on EEC mechanics but also highlight the potential of adult stem cell-derived organoids for studying these elusive cells.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294990702400007X/pdfft?md5=7e7a84b1d3091d22eb0e704bba9d73c7&pid=1-s2.0-S294990702400007X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139873958","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":"Mechanotransduction in distinct F-actin architectures: a novel molecular tension sensor revealing cellular mechanical anisotropy","authors":"Ting Liang, Bin Li","doi":"10.1016/j.mbm.2024.100045","DOIUrl":"10.1016/j.mbm.2024.100045","url":null,"abstract":"<div><p>Mechanotransduction is essential for cell fate and behavior, and F-actin plays a key role in the generation and transmission of molecular forces. A recent study published in <em>Nature Communication</em> presented a novel high-precision molecular tension measurement method using a Förster resonance energy transfer–based tension sensor with separated load-bearing function within distinct F-actin structures, and demonstrated that cellular mechanical anisotropy depends on cell shape, loading direction, and magnitude.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 1","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000081/pdfft?md5=bf931c2754476d0bbf59edb231c0f974&pid=1-s2.0-S2949907024000081-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139880681","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}
Rui Feng , Wenhui Hu , Yuheng Li , Xuan Yao , Jianmei Li , Xiaoming Li , Jing Zhang , Yu Wu , Fei Kang , Shiwu Dong
{"title":"Mechanotransduction in subchondral bone microenvironment and targeted interventions for osteoarthritis","authors":"Rui Feng , Wenhui Hu , Yuheng Li , Xuan Yao , Jianmei Li , Xiaoming Li , Jing Zhang , Yu Wu , Fei Kang , Shiwu Dong","doi":"10.1016/j.mbm.2024.100043","DOIUrl":"10.1016/j.mbm.2024.100043","url":null,"abstract":"<div><p>Osteoarthritis (OA) is a progressive degenerative joint sickness related with mechanics, obesity, ageing, <em>etc</em>., mainly characterized by cartilage degeneration, subchondral bone damage and synovium inflammation. Coordinated mechanical absorption and conduction of the joint play significant roles in the prevalence and development of OA. Subchondral bone is generally considered a load-burdening tissue where mechanosensitive cells are resident, including osteocytes, osteoblast lineage cells, and osteoclast lineage cells (especially less concerned in mechanical studies). Mechano-signaling imbalances affect complicated cellular events and disorders of subchondral bone homeostasis. This paper will focus on the significance of mechanical force as the pathogenesis, involvement of various mechanical force patterns in mechanosensitive cells, and mechanobiology research of loading devices <em>in vitro</em> and <em>in vivo</em>, which are further discussed. Additionally, various mechanosensing structures (<em>e.g</em>., transient receptor potential channels, gap junctions, primary cilia, podosome-associated complexes, extracellular vesicles) and mechanotransduction signaling pathways (<em>e.g</em>., Ca<sup>2+</sup> signaling, Wnt/β-catenin, RhoA GTPase, focal adhesion kinase, cotranscriptional activators YAP/TAZ) in mechanosensitive bone cells. Finally, we highlight potential targets for improving mechanoprotection in the treatment of OA. These advances furnish an integration of mechanical regulation of subchondral bone homeostasis, as well as OA therapeutic approaches by modulating mechanical homeostasis.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 2","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000068/pdfft?md5=2456e3a7b55c2a6f548d64379791d3e8&pid=1-s2.0-S2949907024000068-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139817437","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 impact on biomineralization: Enhancing the strength of composite materials","authors":"Xufeng Niu , Chunyang Ma , Yubo Fan","doi":"10.1016/j.mbm.2024.100042","DOIUrl":"https://doi.org/10.1016/j.mbm.2024.100042","url":null,"abstract":"<div><p>A recent study published in Nature Communications introduces a novel mechanically-mediated reaction involving ZnO nanoparticles that autonomously react, forming Zn/S mineral microrods within an organogel. These microrods selectively reinforce synthetic polymer composites, offering a unique approach to material strengthening. The method provides a distinctive pathway for mechanical mineralization in composite materials.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 1","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000056/pdfft?md5=c47df0d8e24d3f9e5042823d5f466916&pid=1-s2.0-S2949907024000056-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139709567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanobiology of Type 1 hypersensitivity: Elucidating the impacts of mechanical forces in allergic reactions","authors":"Henry Sutanto","doi":"10.1016/j.mbm.2024.100041","DOIUrl":"https://doi.org/10.1016/j.mbm.2024.100041","url":null,"abstract":"<div><p>Type 1 hypersensitivity involves an exaggerated immune reaction triggered by allergen exposure, leading to rapid release of inflammatory mediators. Meanwhile, mechanobiology explores how physical forces influence cellular processes, and recent research underscores its relevance in allergic reactions. This review provides a concise overview of Type 1 hypersensitivity, highlighting the pivotal role of mast cells and immunoglobulin E (IgE) antibodies in orchestrating allergic reactions. Recognizing the dynamic nature of cellular responses in allergies, this study subsequently delves into the emerging field of mechanobiology and its significance in understanding the mechanical forces governing immune cell behavior. Furthermore, molecular forces during mast cell activation and degranulation are explored, elucidating the mechanical aspects of IgE binding and cytoskeletal rearrangements. Next, we discuss the intricate interplay between immune cells and the extracellular matrix, emphasizing the impact of matrix stiffness on cellular responses. Additionally, we examine key mechanosensitive signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway, Rho guanosine triphosphatase (GTPase) and integrin-mediated focal adhesion signaling, shedding light on their contributions to hypersensitivity reactions. This interplay of mechanobiology and Type 1 hypersensitivity provides insights into potential therapeutic targets and biomarkers, paving the way for better clinical management of Type 1 hypersensitivity reactions.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 1","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000044/pdfft?md5=adfe1fafbdc05ac9316b2a18d7522f69&pid=1-s2.0-S2949907024000044-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682632","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}