iProXProteomicsYang ChenMus Musculushttp://www.iprox.org/page/project.html?id=IPX0019159000chenyang1816185048@bjmu.edu.cnThe Center for Precision Medicine Multi-omics Research (CPMMR)iProXfalseStiffness Programs WDR44 Phosphorylation to Gate Cargo Sorting into MigrasomesCells release extracellular vesicles (EVs) for intercellular communication, homeostasis, and microenvironment remodeling, yet how physiological matrix stiffness controls EV cargo sorting remains unclear. Here we show that stiffness programs a cargo-selective sorting pathway in migrasomes, where matrix stiffness couples Integrin β1–FAK–AKT to AKT-dependent phosphorylation of WDR44. Critically, phosphorylated WDR44 acts as a molecular gate that enables Rab11b-dependent trafficking of intraluminal nanovesicles via Myosin Va into migrasomes. Consistently, physiologically stiffness-programmed migrasomes enriched in CSF1 enhance macrophage-recruiting transport and accelerate wound closure in vitro. Together, these findings reveal a mechanistic framework for stiffness-regulated migrasome cargo sorting, and the tunable GA hydrogel platform (300–2,300 Pa) provides a scalable way to guide EV production under defined mechanical conditions.Mon Aug 24 00:00:00 BST 2026PXD08316410090