BPS2026 – Elucidating the structural determinants of integrin mechanosensitivity

Understanding how pathologies are affected by the physical forces acting upon them offers a novel mechanism through which therapies, diagnostic tools, and medicines can be developed. Integrins are a family of heterodimeric transmembrane receptors that serve as essential mechanosensitive molecules, mediating bidirectional signaling between the cell and its environment. They play critical roles in mechanotransduction by translating extracellular mechanical cues into intracellular biochemical signals. Despite their fundamental importance, the mechanosensitivity of integrins—particularly how mechanical force regulates their conformational changes and ligand-binding functions—remains poorly understood. This project focuses on α IIb β 3 and α v β 3 integrins, which share the β 3 subunit but exhibit markedly different force-dependent behaviors in conformational dynamics and ligand binding. Additional α V -containing integrins are also studied to explore the broader spectrum of RGD (arginine, glycine, aspartate)-binding integrin mechanosensitivity. Using single-molecule force spectroscopy my project aims to provide in-depth insights into the structural basis of distinctive mechanosensitivity across different RGD-binding integrins and establish approaches to manipulate integrin mechanosensitivity precisely. Preliminary data has shown that α v β 3 and α V -containing integrins exhibit unique conformation-function decoupling compared to the standard coupling observed in α IIb β 3 . These findings reveal fundamental principles of integrin mechanosensitivity and help lay the groundwork for future mechanotherapeutic development.