{"title":"Decoding force-transmission linkages for therapeutic targeting and engineering.","authors":"Jingzhun Liu, Yunxin Deng, Jie Yan","doi":"10.1063/5.0267032","DOIUrl":null,"url":null,"abstract":"<p><p>Mechanosensing and mechanotransduction enable cells to perceive and respond to mechanical forces, underpinning essential physiological processes and disease pathways. Central to these phenomena are force-transmission supramolecular linkages, which undergo structural transitions and regulate signaling proteins in response to mechanical stimuli. This review examines the mechanisms of these force-bearing linkages, focusing on force duration, dictated by the stability of protein-protein interfaces, and force-dependent mechanical structural changes of force-bearing domains in the linkage, which activates or deactivates mechanosensing domains. We discuss the emerging potential of these linkages as pharmaceutical targets, exploring drugs and peptides designed to modulate these mechanical properties. In addition, we highlight the application of artificial intelligence in protein engineering to enhance therapeutic precision by dynamically tuning these mechanosensing characteristics. Our synthesis of current findings and future perspectives aims to inform novel approaches to drug design and inspire future research in the field of mechanomedicine.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"021504"},"PeriodicalIF":6.6000,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166987/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"APL Bioengineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1063/5.0267032","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Mechanosensing and mechanotransduction enable cells to perceive and respond to mechanical forces, underpinning essential physiological processes and disease pathways. Central to these phenomena are force-transmission supramolecular linkages, which undergo structural transitions and regulate signaling proteins in response to mechanical stimuli. This review examines the mechanisms of these force-bearing linkages, focusing on force duration, dictated by the stability of protein-protein interfaces, and force-dependent mechanical structural changes of force-bearing domains in the linkage, which activates or deactivates mechanosensing domains. We discuss the emerging potential of these linkages as pharmaceutical targets, exploring drugs and peptides designed to modulate these mechanical properties. In addition, we highlight the application of artificial intelligence in protein engineering to enhance therapeutic precision by dynamically tuning these mechanosensing characteristics. Our synthesis of current findings and future perspectives aims to inform novel approaches to drug design and inspire future research in the field of mechanomedicine.
期刊介绍:
APL Bioengineering is devoted to research at the intersection of biology, physics, and engineering. The journal publishes high-impact manuscripts specific to the understanding and advancement of physics and engineering of biological systems. APL Bioengineering is the new home for the bioengineering and biomedical research communities.
APL Bioengineering publishes original research articles, reviews, and perspectives. Topical coverage includes:
-Biofabrication and Bioprinting
-Biomedical Materials, Sensors, and Imaging
-Engineered Living Systems
-Cell and Tissue Engineering
-Regenerative Medicine
-Molecular, Cell, and Tissue Biomechanics
-Systems Biology and Computational Biology