Convection and extracellular matrix binding control interstitial transport of extracellular vesicles

Abstract

Extracellular vesicles (EVs) influence a host of normal and pathophysiological processes in vivo. Compared to soluble mediators, EVs are relatively large (~30-150 nm) and can traffic a wide range of proteins on their surface including extracellular matrix (ECM) binding proteins. We isolated EVs from the MCF10 series - a model human cell line of breast cancer progression - and demonstrated increasing presence of laminin-binding integrins 3{beta}1 and 6{beta}1 on the EVs as the malignant potential of the MCF10 cells increased. Transport of the EVs within a microfluidic device under controlled physiological interstitial flow (0.15-0.75 m/s) demonstrated that convection was the dominant mechanism of transport. Binding of the EVs to the ECM enhanced the spatial concentration and gradient, which was partially mitigated by blocking integrins 3{beta}1 and 6{beta}1. Our studies demonstrate that convection and ECM binding are the dominant mechanisms controlling EV interstitial transport and should be leveraged in the design of nanotherapeutics.