Mechanical strength and biomechanics of extracellular vesicles

Extracellular vesicles (EVs) serve as essential mediators of intercellular communication and play a pivotal role in both physiological and pathological processes. Their mechanical strength and biomechanical properties not only dictate structural stability, in vivo delivery efficiency, and biological functionality but also have significant implications for disease diagnosis and targeted therapy. This review systematically summarizes the methodologies and key parameters used to assess the mechanical strength of EVs, and synthesizes current evidence identifying the internal protein network, membrane cholesterol and phospholipid composition, AQP1 and other membrane protein expression levels, and vesicle size differences as primary structural determinants of EV elasticity. Furthermore, the physiological state of the source cells, production processes, and external mechanical forces are also recognized as critical factors shaping EV mechanical properties. In addition, this review comprehensively discusses the adaptive behaviors of EVs with distinct mechanical characteristics in complex biological environments, with a particular focus on their transmembrane transport, circulation dynamics, and targeted delivery capabilities, and delineates the mechanistic principles by which EVs with varying elasticity achieve prolonged circulation and subsequent uptake by recipient cells. Based on recent advances, this review also explores the potential applications of the mechanical properties and biomechanical principles of EVs in quality control assessment, disease diagnostics, and drug delivery, while offering a forward-looking perspective on their future development in the biomedical field.