Zhenkang Wen , Lei Lei , Haozhi Zhang , Zheyu Jin , Zhengming Shan , Weiyang Liu , Wenxue Tong , Jiankun Xu , Ling Qin
{"title":"Magnesium-containing implants enhance bone healing: A mechanobiological perspective","authors":"Zhenkang Wen , Lei Lei , Haozhi Zhang , Zheyu Jin , Zhengming Shan , Weiyang Liu , Wenxue Tong , Jiankun Xu , Ling Qin","doi":"10.1016/j.mbm.2025.100161","DOIUrl":"10.1016/j.mbm.2025.100161","url":null,"abstract":"<div><div>Unlike traditional implants primarily composed of bioinert materials, magnesium (Mg) -a degradable biomaterial - offers significant promise for next-generation bone healing implants, whether utilized as a primary structural component or a supporting material. While most research focuses on Mg's bioactive and osteoimmunological effect, this review highlights its mechanobiological role, summarizing the merits of Mg-containing implants in facilitating mechanotransduction and associated cellular events during the bone healing. Beyond introducing Mg's biomechanical benefits in preventing stress shielding, this review synthesizes its unique attributes: exceptional bone-implant integration and synergistic effects with physical stimuli to amplify new bone formation. Crucially, we also summarize the activation of mechanotransduction signaling pathways, providing a mechanistic basis for Mg's positive mechanobiological influence. Finally, we discuss challenges arising from the interaction between physical loading and Mg degradation, alongside future perspectives and potential solutions to bridge the gap between theory and clinical application, thereby accelerating translation applications of Mg-containing implants.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 4","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthetic mechanoreceptor engineering: From genetic encoding to DNA nanotechnology-based reprogramming","authors":"Sihui Yang , Zhou Nie","doi":"10.1016/j.mbm.2025.100160","DOIUrl":"10.1016/j.mbm.2025.100160","url":null,"abstract":"<div><div>Precise modulation of mechanoreceptor-mediated signal transduction is crucial for decoding cellular mechanotransduction mechanisms and programming cell fate. This review provides a comprehensive summary of recent advances in engineering synthetic mechanoreceptors, spanning from protein-centric genetic encoding to DNA nanotechnology-based non-genetic reprogramming strategies. Genetic engineering strategies employ protein structure encoding and site-directed mutagenesis to reprogram force-response functions in natural mechanoreceptors. As a complementary non-genetic approach, DNA nanotechnology leverages its programmability, modularity, and predictable mechanical properties to achieve precise control over receptor functionalities. The flourishing development of DNA mechanosensitive nanodevices has provided a promising synthetic toolkit for manipulating mechanoreceptors, enabling precise control over receptor spatial organization and signal transduction. A key innovation is the development of novel DNA-functionalized artificial mechanoreceptors (AMRs), which confer force-responsiveness to naturally non-mechanosensitive receptors without genetic modification, thereby enabling customized mechanotransduction and mechanobiological applications. Collectively, this paradigm shift highlights DNA-based non-genetic receptor engineering as a versatile and powerful toolkit, paving new avenues for mechanobiology research and pioneering force-directed therapeutic strategies in regenerative medicine.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 4","pages":"Article 100160"},"PeriodicalIF":0.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qifan Yu , Yudong Duan , Zhuang Zhu , Wei Ji , Caihong Zhu , Bin Li
{"title":"Multimodal mechanoregulation strategies towards tissue regeneration","authors":"Qifan Yu , Yudong Duan , Zhuang Zhu , Wei Ji , Caihong Zhu , Bin Li","doi":"10.1016/j.mbm.2025.100159","DOIUrl":"10.1016/j.mbm.2025.100159","url":null,"abstract":"<div><div>Mechanical microenvironment of each tissue plays an important role in regulating its special cellular behaviors, such as morphology, proliferation, differentiation, and migration. Mechanical signals can direct lineage specification or promote cell migration towards injury sites and facilitate tissue repair. During tissue regeneration, mechanoregulation is also important due to the ability of providing an extracellular microenvironment that closely resembles the physiological state for cells. Currently, mechanoregulation strategies have been usually applied to promote tissue regeneration. However, the <em>in vivo</em> mechanical environment is highly complex, these single mechanical conditioning strategies cannot comprehensively replicate the mechanical microenvironment experienced by cells or tissues in the body, thereby hindering the achievement of efficient tissue regeneration. The proposal of multimodal mechanoregulation strategies offers promising avenues to address this limitation. Herein, we summarize the critical role of mechanical factors in promoting tissue regeneration and the current development of different multimodal mechanoregulation approaches. Furthermore, the complex mechanical microenvironment of various tissues such as bone, intervertebral disc and cardiac. Afterwards, the recent successful applications of multimodal mechanical strategies in regenerative therapies were reviewed. And we delineate the persisting challenges, potential resolutions, and emerging translational prospects for multimodal mechanoregulation strategies in regenerative medicine, providing a reference for further development of multimodal mechanoregulation approaches.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 4","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirko D'Urso , Pim van den Bersselaar , Sarah Pragnere , Paolo Maiuri , Carlijn V.C. Bouten , Nicholas A. Kurniawan
{"title":"Substrate stiffness modulates phenotype-dependent fibroblast contractility and migration independent of TGF-β stimulation","authors":"Mirko D'Urso , Pim van den Bersselaar , Sarah Pragnere , Paolo Maiuri , Carlijn V.C. Bouten , Nicholas A. Kurniawan","doi":"10.1016/j.mbm.2025.100158","DOIUrl":"10.1016/j.mbm.2025.100158","url":null,"abstract":"<div><div>During wound healing, fibroblasts undergo radical processes that impact their phenotype and behavior. They are activated, recruited to the injury site, assume a contractile phenotype, and secrete extracellular matrix proteins to orchestrate tissue repair. Thus, fibroblast responses require dynamic changes in cytoskeleton assembly and organization, adhesion morphology, and force generation. At the same time, fibroblasts experience changes in environmental stiffness during tissue wounding and healing. Although cells are generally known to use their adhesion–contraction machinery to sense microenvironmental stiffness, little is known about how stiffness affects the fibroblast phenotypical transition and behavior in wound healing. Here we demonstrate that stiffness plays a deterministic role in determining fibroblast phenotype, surprisingly even overruling the classical TGF-<em>β</em>-mediated stimulation. By combining morphometric analysis, traction force microscopy, and single-cell migration analysis, we show that environmental stiffness primes the cytoskeletal and mechanical responses of fibroblasts, strongly modulating their morphology, force generation, and migration behavior. Our study, therefore, points to the importance of tissue stiffness as a key mechanobiological regulator of fibroblast behavior, thus serving as a potential target for controlling tissue repair.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 4","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanotransduction in neutrophil: Mechanosensing and immune function regulation","authors":"Wenying Zhao, Jin Wang, Jing Wang","doi":"10.1016/j.mbm.2025.100157","DOIUrl":"10.1016/j.mbm.2025.100157","url":null,"abstract":"<div><div>Immune cells sense and transduce mechanical signals such as stiffness, stretch, compression, and shear stress. In the past few years, our understanding of the mechanosensitive signaling pathways in myeloid cells has significantly expanded, especially in monocytes, macrophages, and dendritic cells. Recently, the mechanobiological regulation of neutrophil function has been deciphered. Mechanical signals from tissue-derived shear stress and cellular deformation tension reprogram neutrophil transcription via GEF-H1, PIEZO1, and TRPV4 pathways, modulating neutrophil functions in homeostasis and trans-endothelial migration. Understanding these force-dependent processes provides novel insights into neutrophil plasticity and highlights potential therapeutic strategies and approaches for inflammatory and infectious diseases.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 4","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Allosteric pockets in the measles and Nipah virus polymerases: Mechanobiological insights and AI-driven drug discovery opportunities","authors":"Yiru Wang , Lixia Zhao , Heqiao Zhang","doi":"10.1016/j.mbm.2025.100156","DOIUrl":"10.1016/j.mbm.2025.100156","url":null,"abstract":"<div><div>Nonsegmented negative-sense RNA viruses (nsNSVs)—including highly pathogenic pathogens such as measles virus (MeV), Nipah virus (NiV), Hendra virus (HeV), Ebola virus (EBOV), and others—pose major global health threats, yet most lack approved antiviral therapeutics. In the recent study, high-resolution cryo-electron microscopy (cryo-EM) revealed previously unrecognized allosteric pockets in the large (L) polymerase proteins of MeV and NiV, spatially distinct from the catalytic nucleotide-binding site. We further demonstrated that the non-nucleoside inhibitor ERDRP-0519 engages these pockets to allosterically ‘lock’ the polymerase in a mechanically inactive state. These findings reveal an allosteric mechanism of inhibition rooted in the conformational mechanics of the enzyme and highlight opportunities for integrating artificial intelligence (AI)-aided drug discovery (AIDD) into rational drug design.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 4","pages":"Article 100156"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Theta-shaking mitigates cognitive-emotional decline via subiculum and ventral septum metabolic plasticity","authors":"Runhong Yao , Kouji Yamada , Hirohide Sawada , Takeshi Chihara , Naoki Aizu , Kazuhiro Nishii","doi":"10.1016/j.mbm.2025.100148","DOIUrl":"10.1016/j.mbm.2025.100148","url":null,"abstract":"<div><div>Aging-associated cognitive decline remains a major challenge in gerontology; few non-invasive interventions provide both mechanistic insight and translational feasibility. We investigated whether low-frequency “theta-shaking” whole-body vibration (5 Hz) could modulate cognitive function, emotional behavior, and metabolic plasticity in a senescence-accelerated mouse model. Senescence-accelerated mouse prone-10 mice were exposed to theta-shaking stimulation for 30 weeks. Spatial memory was assessed using Y-maze spontaneous alternation test, and anxiety-related behavior was evaluated using marble burying test. Histological and immunohistochemical analyses were conducted to assess neuronal density and protein expression in specific brain regions. Theta-shaking subjected mice exhibited delayed yet significant improvements in spatial memory at 20 (p = 0.017) and 30 (p = 0.018) weeks. Anxiety-related behavior shows a biphasic pattern: an initial increase at 20 weeks (p < 0.001) followed by stabilization at 30 weeks. Histological analysis revealed preserved neuronal density in the subiculum (p < 0.001) and elevated proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression in the Cornu Ammonis 1, subiculum, and lateral septum (all p < 0.05). Notably, mitochondrial biogenesis appeared to be intervention's primary target, as shown by robust PGC1α upregulation, while brain-derived neurotrophic factor revealed a trend-level increase (p = 0.062), and neurotrophin-3 expression remained unchanged. Frequency-tuned mechanical stimulation induced region-specific neural neurometabolic adaptations, supporting theta-shaking as a non-pharmacological, low-exertion strategy to counteract brain aging. These findings offer promising translational potential, especially for individuals with limited mobility.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 4","pages":"Article 100148"},"PeriodicalIF":0.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fighting cardiac fibrosis using the chemomechanical method","authors":"Yunlong Huo","doi":"10.1016/j.mbm.2025.100147","DOIUrl":"10.1016/j.mbm.2025.100147","url":null,"abstract":"<div><div>Diffuse myocardial fibrosis affects disease severity and outcomes in multiple heart diseases. A recent study in NATURE has shown a chemomechanical method to regulate myocardial stromal cell states to suppress fibrosis in vitro and in vivo, which provides a proof-of-concept therapeutic strategy. This study reviews the proposed chemomechanical method and other recent biotechnologies to fight cardiac fibrosis.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100147"},"PeriodicalIF":0.0,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondria power the nucleus under pressure","authors":"Meng Yao , Yao Zong , Junjie Gao","doi":"10.1016/j.mbm.2025.100146","DOIUrl":"10.1016/j.mbm.2025.100146","url":null,"abstract":"<div><div>Mechanical confinement of cells, as occurs during processes like tumor cell invasion or immune cell trafficking, poses a pressure that can threaten nuclear integrity and cell viability. Recent findings illuminate a rapid adaptive mechanism by which cells under acute compressive stress rearrange their internal architecture to preserve nuclear functions. Upon confinement, mitochondria swiftly relocate to cluster around the nucleus (forming nuclear-associated mitochondria, NAM), entrapped by a web of endoplasmic reticulum (ER) and actin filaments. This proximity provides a localized surge of ATP within the nucleus, fueling energy-intensive nuclear processes, notably maintaining an open chromatin state and facilitating efficient DNA damage repair. This targeted energy delivery maintains nuclear chromatin accessibility, supports DNA repair mechanisms, and ensures sustained cell proliferation despite physical constraints. Here we provide a commentary on these findings, discussing the biological significance of mitochondria–nucleus repositioning, the role of nuclear ATP in safeguarding chromatin, and the broader implications for cellular fitness in development and disease.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100146"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gurneet S. Sangha , Lauren V. Smith , Marzyeh Kheradmand , Kashif M. Munir , Nimisha Rangachar , Callie M. Weber , Zohreh Safari , Stephen C. Rogers , Allan Doctor , Alisa Morss Clyne
{"title":"Piezo1 activates nitric oxide synthase in red blood cells via protein kinase C with increased activity in diabetes","authors":"Gurneet S. Sangha , Lauren V. Smith , Marzyeh Kheradmand , Kashif M. Munir , Nimisha Rangachar , Callie M. Weber , Zohreh Safari , Stephen C. Rogers , Allan Doctor , Alisa Morss Clyne","doi":"10.1016/j.mbm.2025.100145","DOIUrl":"10.1016/j.mbm.2025.100145","url":null,"abstract":"<div><div>Nitric oxide (NO) is a key signaling molecule in maintaining cardiovascular health. While endothelial cells were initially thought to exclusively contain endothelial nitric oxide synthase (eNOS), an enzyme that produces NO, recent evidence suggests that red blood cells (RBC) also contain functional eNOS that impacts cardiovascular function. However, the mechanisms driving RBC eNOS activation are not well understood. Like endothelial cells, RBC are mechanosensitive via the stretch-activated piezo1 Ca<sup>2+</sup> channel. Therefore, we investigated how piezo1 stimulation induced RBC and endothelial eNOS phosphorylation. We further examined how this mechanism is affected during diabetes, a condition known to impair vascular NO bioavailability. Our results reveal that piezo1 stimulation activated RBC eNOS via protein kinase C (PKC) and endothelial eNOS partially via protein kinase B (Akt). Surprisingly, piezo1-stimulation increased eNOS phosphorylation at the Ser1177 activation site nearly 20-fold in RBC from diabetic patients compared to 5.5-fold in RBC from non-diabetic patients. These findings highlight important differences in eNOS activation between RBC and endothelial cells and suggest potential biomolecular markers for targeting vascular NO bioavailability in health and disease.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}