Unraveling the physical interactions of extracellular vesicles in tissues

Extracellular vesicles (EVs) are critical nanoscale carriers of intercellular signals and bioactive molecules, yet their physical behavior in complex tissue environments remains underexplored, particularly from the perspective of soft matter physics. This talk examines the mechanical properties, transport dynamics, and interactions of EVs within extracellular matrices and target cells, with significant implications for their therapeutic applications. EVs must navigate dense, nanoporous extracellular matrices, where their movement is governed by the viscoelastic properties of the matrix, which influence their diffusivity and transport efficiency. Additionally, aquaporin-mediated water permeation enhances EV deformability, facilitating efficient transport through confined environments such as hydrogels and decellularized tissues. Beyond transport, the physical interactions between EV membranes and target cells are essential for activating cell signaling over distances. The talk will also explore how engineered EVs, modified to present specific ligands like Notch signaling molecules, interact with cells under fluid shear stress to promote vascular repair—an effect that standard synthetic liposomes cannot achieve. The ability of EVs to restore endothelial junctions and vascular integrity highlights their therapeutic potential, which relies on both the mechanical properties of the EV membrane and the surrounding environment. This work bridges soft matter physics, nanoscale mechanics, and therapeutic development, providing new insights into the role of EVs in tissue regeneration and repair.