Breast cancer cell-derived extracellular vesicles accelerate collagen fibrillogenesis and integrate into the matrix

Though extracellular vesicles (EVs) contain much of the cellular machinery required for actively remodeling extracellular matrix (ECM), they are mostly appreciated for their roles in reprogramming cell proxies. Using a bottom-up biomimetic system, we show that breast cancer cell-derived EVs at the nanoscale can play an active role in collagen I matrix formation at the microscale. EVs nucleate new fibrils, recruiting collagen molecules from solution and enhancing fibril growth and network formation, resulting in more densely packed matrices with significantly increased storage and loss moduli. These effects are specific to EV membrane composition and cannot be reproduced using trypsinized EVs, synthetic liposomes, or mechanically extruded plasma membrane material. EVs become integrated into the fibril structures that they help form, reminiscent of matrix vesicles found within tissues. This represents a plausible way by which EVs are deposited into the ECM, becoming signaling cues for resident cells.