Extracellular vesicles (EVs) constitute a diverse family, with major subtypes including exosomes (30–150 nm), released through fusion of multivesicular bodies with the cell membrane; microvesicles (100–1000 nm), generated by budding from the plasma membrane; and apoptotic bodies (500–2000 nm), formed by the disintegration of apoptotic cells [1]. Additionally, other subtypes such as large vesicles (>1000 nm), elongated particles (50–500 nm), and supramolecular attack particles are also recognized [2]. These EVs play a pivotal role in cell biology, including the transport and recycling of intracellular and membrane proteins, intercellular transfer of proteins, nucleic acids, and metabolites, and the transmission of neural signals [3], [4]. Consequently, EVs, which carry critical biological information, not only serve as essential mediators of cellular communication but also hold great potential as biomarkers and therapeutic delivery vehicles, with significant applications in the diagnosis and treatment of various diseases [5], [6].
Biomechanics is the study of the mechanical properties and response behaviors of materials or biological tissues under external forces, encompassing structural stability, deformation, and mechanical regulation mechanisms across molecular to macroscopic scales [7]. The mechanical strength of EVs plays a crucial role in adapting to the biomechanical characteristics of the body, significantly influencing their biological function and applications. These mechanical properties directly impact the stability of EVs in circulation, their tissue penetration ability, and the efficiency of phagocytosis and recognition by target cells [8], [9]. For instance, EVs with higher mechanical strength exhibit enhanced stability in the bloodstream, while better deformability facilitates their transport through complex tissue microenvironments. Furthermore, EVs derived from different sources can inherit some of the mechanical properties of their parent cells, reflecting pathological states, thus serving as valuable diagnostic biomarkers. Therefore, elucidating the mechanical performance and general biomechanical principles of EVs is essential for optimizing their applications in drug delivery, disease diagnosis, and therapeutic strategies.
This review begins with the measurement techniques and key parameters of EV mechanical properties, systematically analyzing the structural features and environmental factors that influence their mechanical performance. It further summarizes the biomechanical principles of EVs in vivo (Fig. 1). The article also highlights recent advancements in the application of EVs in disease diagnosis and precision medicine, guided by these principles, revealing their vast potential and translational value in the medical field. Overall, this work provides a forward-looking perspective for expanding the application prospects of EVs based on biomechanical principles and lays a theoretical foundation and guiding framework for the clinical translation of vesicle-based designs.