Mechanobiology in Medicine最新文献

{"title":"Allosteric pockets in the measles and Nipah virus polymerases: Mechanobiological insights and AI-driven drug discovery opportunities","authors":"Yiru Wang ,&nbsp;Lixia Zhao ,&nbsp;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 ,&nbsp;Kouji Yamada ,&nbsp;Hirohide Sawada ,&nbsp;Takeshi Chihara ,&nbsp;Naoki Aizu ,&nbsp;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 ​&lt; ​0.001) followed by stabilization at 30 weeks. Histological analysis revealed preserved neuronal density in the subiculum (p ​&lt; ​0.001) and elevated proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression in the Cornu Ammonis 1, subiculum, and lateral septum (all p ​&lt; ​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 ,&nbsp;Yao Zong ,&nbsp;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}

{"title":"Piezo1 activates nitric oxide synthase in red blood cells via protein kinase C with increased activity in diabetes","authors":"Gurneet S. Sangha ,&nbsp;Lauren V. Smith ,&nbsp;Marzyeh Kheradmand ,&nbsp;Kashif M. Munir ,&nbsp;Nimisha Rangachar ,&nbsp;Callie M. Weber ,&nbsp;Zohreh Safari ,&nbsp;Stephen C. Rogers ,&nbsp;Allan Doctor ,&nbsp;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 Ca²⁺ 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}

{"title":"Three-dimensional spheroid models for cardiovascular biology and pathology","authors":"Alanna Krug ,&nbsp;Gabrielle Inserra ,&nbsp;Rhonda Drewes ,&nbsp;Amanda Krajnik ,&nbsp;Joseph A. Brazzo III ,&nbsp;Thomas Mousso ,&nbsp;Su Chin Heo ,&nbsp;Yongho Bae","doi":"10.1016/j.mbm.2025.100144","DOIUrl":"10.1016/j.mbm.2025.100144","url":null,"abstract":"<div><div>Scaffold-free three-dimensional (3D) cellular spheroid cultures better replicate the <em>in vivo</em> cellular microenvironments of complex tissues than traditional two-dimensional (2D) cell cultures, as they promote more intricate cell-cell and cell-extracellular matrix (ECM) interactions. In the context of cardiovascular research, 3D spheroids have emerged as valuable models for studying angiogenesis, modeling the cardiac microenvironment, and advancing drug development and cardiac tissue repair. Given that cardiovascular disease remains the leading cause of morbidity worldwide, exploring 3D spheroids as <em>in vitro</em> models in cardiovascular research holds potential for advancing the field. Despite their promise, the experimental potential of 3D spheroids in cardiovascular disease and biology has yet to be realized. Therefore, this review discusses the advantages and limitations of 3D spheroid models for studying angiogenesis and cardiovascular pathobiology, their applications in cardiac drug development and tissue repair, and how these models can advance cardiovascular research.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535580","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":"Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine","authors":"Ruobing Liu ,&nbsp;Yaru Huang ,&nbsp;Maogang Jiang ,&nbsp;Fei Xu ,&nbsp;Qilin Pei ,&nbsp;Jiajun Ma ,&nbsp;Youru Li ,&nbsp;Siqi Shen ,&nbsp;Bo Zhang ,&nbsp;Xiangyang Guo ,&nbsp;Jing Cai ,&nbsp;Wenwen Wang","doi":"10.1016/j.mbm.2025.100137","DOIUrl":"10.1016/j.mbm.2025.100137","url":null,"abstract":"<div><div>Blood metabolomes have been linked to osteoporosis, yet the precise causal relationship with osteopenia, its preventable early stage, remains unclear. This study aimed to uncover the genetic causality between blood metabolomes and osteopenia, pinpointing potential targets for mechanomedicine. Utilizing genome-wide association study summary statistics, we analyzed 1091 metabolites and 309 metabolite ratios from 8299 individuals, correlating them with total body bone mineral density (BMD) from 56,284 individuals in the IEU GWAS database and osteopenia data from 408,961 European populations. Through two-sample Mendelian randomization, we investigated the association between blood metabolomes and skeletal characteristics. We then conducted summary-data-based Mendelian randomization (MR) analysis and colocalization analyses to identify causal genes related to skeletal phenotypes, predicting therapeutic targets for osteopenia. Expression of potential targets in osteocytes under fluid shear stress (FSS) stimulation was tested using qRT-PCR to explore mechanical sensitivity and bone health mechanisms. Our findings revealed five metabolites affecting total body BMD and osteopenia, with biliverdin emerging as a potential protective factor against osteopenia (OR ​= ​0.93, 95 ​%CI ​= ​0.88–0.98, <em>P</em> ​= ​0.009). Additionally, three genes—LRRC14, SLC22A16, and TNFRSF1A—were identified as potential therapeutic targets for osteopenia. Notably, LRRC14 and TNFRSF1A are also associated with other musculoskeletal diseases. In vitro experiments showed that FSS significantly increased LRRC14 expression in osteocytes, suggesting its potential as a mechanosensitive factor. This study identifies candidate blood metabolites and mechanomedicine targets for osteopenia, offering a scientific basis for new diagnostic and treatment strategies and deepening our understanding of bone mechanics response characteristics.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100137"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296837","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":"Beyond biochemical patterning: How mechanical bistability governs robust organoid morphogenesis","authors":"Qigan Gao,&nbsp;Yuehua Yang,&nbsp;Haoxiang Yang,&nbsp;Hongyuan Jiang","doi":"10.1016/j.mbm.2025.100134","DOIUrl":"10.1016/j.mbm.2025.100134","url":null,"abstract":"<div><div>Understanding the regulatory mechanisms of intestinal organoid morphogenesis remains a fundamental challenge in organoid biology. Emerging evidence highlights mechanical bistability as a critical regulator, mediated by dynamic lumen-actomyosin feedback. The recently developed 3D vertex model demonstrates that crypt curvature modulates actomyosin localization via mechanosensitive pathways, creating two stable morphological states—bulged or budded—depending on mechanical history. This model advances beyond static vertex models by incorporating epithelial thickness variations and lumen pressure effects, explaining previously unresolved phenomena like irreversible crypt budding and snap-through transitions. The findings establish a new framework for understanding mechanical decision-making in epithelial tissues, with implications for organoid engineering and developmental biology.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 2","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184941","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":"Early diabetes screening via red blood cell mechanics using microfluidic chip integration","authors":"Yibo Feng ,&nbsp;Bingchen Che ,&nbsp;Yonggang Liu ,&nbsp;Cangmin Zhang ,&nbsp;Jiameng Niu ,&nbsp;Jiangcun Yang ,&nbsp;Guangyin Jing ,&nbsp;Dan Sun ,&nbsp;Xiaobo Gong ,&nbsp;Ce Zhang","doi":"10.1016/j.mbm.2025.100136","DOIUrl":"10.1016/j.mbm.2025.100136","url":null,"abstract":"<div><div>Early diagnosis of diabetes is crucial, as diabetes, particularly type 2, can eventually lead to irreversible changes and complications. Conventional techniques, such as the Fasting Plasma Glucose (FPG) Test and Hemoglobin A1c (HbA1c) Test, measure blood glucose levels, which fluctuate over time and are insensitive to early stages. In this study, we focus on measuring the mechanical properties of red blood cells, as their irreversible changes can indicate early pathological impacts of diabetes. We developed a microfluidic chip with a symmetrical hyperbolic structure. By periodically altering the state of the valve membrane, we generate a reciprocating shear flow field that repeatedly acts on groups of RBCs. We then quantify the morphological parameters of the RBCs, establishing a correlation between the reciprocating shear flow field and the morphological changes of the cells. Using the developed microfluidic chip, we investigated the resistance of blood cells from 20 healthy volunteers to mechanical stimuli. The results indicated a significant correlation between the deformability of red blood cells and age, while no such correlation was found among individuals of the same gender. This study highlights the potential of utilizing the mechanical properties of red blood cells as an early diagnostic tool for diabetes. Furthermore, given the ease of integration of microfluidic chips, they present a promising high-throughput diagnostic solution for large-scale clinical screening.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 3","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242828","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":"Mechanosensitive nuclear checkpoint: nuclear envelope as a sensor of chromosomal instability and driver of cell fate","authors":"Chenyang Ji,&nbsp;Junwei Chen,&nbsp;Fuxiang Wei","doi":"10.1016/j.mbm.2025.100135","DOIUrl":"10.1016/j.mbm.2025.100135","url":null,"abstract":"<div><div>The nuclear envelope (NE) is a dynamic, mechanosensitive structure that functions as a protective barrier for the genome and serves as a checkpoint responding to external stimuli. It plays a critical role in maintaining genomic stability and regulating cell fate. This review synthesizes recent research highlighting the role of NE as a mechanical checkpoint in ensuring accurate chromosome segregation, regulating cell cycle progression, and contributing to cancer development. Chromosome mis-segregation during cell division is a major driver of aneuploidy, a condition closely associated with genomic instability and cellular transformation. The role of NE in chromatin organization and gene expression regulation is also discussed, underscoring its importance in cell differentiation and identity.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 2","pages":"Article 100135"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168768","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}