Liu Jingzhun, Deng Yunxin, Yan Jie
Department of Physics, National University of Singapore, Singapore 117542, Singapore.
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
APL Bioeng. 2025 Jun 13;9(2):021504. doi: 10.1063/5.0267032. eCollection 2025 Jun.
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.
机械传感和机械转导使细胞能够感知并响应机械力，这是基本生理过程和疾病通路的基础。这些现象的核心是力传递超分子连接，其会经历结构转变并响应机械刺激调节信号蛋白。本综述探讨了这些受力连接的机制，重点关注由蛋白质-蛋白质界面稳定性决定的力持续时间，以及连接中受力结构域的力依赖性机械结构变化，这些变化会激活或失活机械传感结构域。我们讨论了这些连接作为药物靶点的新兴潜力，探索旨在调节这些机械特性的药物和肽。此外，我们强调了人工智能在蛋白质工程中的应用，通过动态调整这些机械传感特性来提高治疗精度。我们对当前研究结果和未来展望的综合旨在为药物设计的新方法提供信息，并激发机械医学领域的未来研究。
