1. Convection and extracellular matrix binding control interstitial transport of extracellular vesicles
- Author
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Sariano, Peter A, Mizenko, Rachel R, Shirure, Venktesh S, Brandt, Abigail K, Nguyen, Bryan B, Nesiri, Cem, Shergill, Bhupinder S, Brostoff, Terza, Rocke, David M, Borowsky, Alexander D, Carney, Randy P, and George, Steven C
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,Breast Cancer ,Humans ,Laminin ,Convection ,Integrin alpha6beta1 ,Extracellular Vesicles ,Integrin alpha3beta1 ,Extracellular Matrix ,diffusion ,exosome ,gradient ,integrin binding ,spatial concentration ,Biochemistry and cell biology - Abstract
Extracellular vesicles (EVs) influence a host of normal and pathophysiological processes in vivo. Compared to soluble mediators, EVs can traffic a wide range of proteins on their surface including extracellular matrix (ECM) binding proteins, and their large size (∼30-150 nm) limits diffusion. We isolated EVs from the MCF10 series-a model human cell line of breast cancer progression-and demonstrated increasing presence of laminin-binding integrins α3β1 and α6β1 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 μm/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 mitigated by blocking integrins α3β1 and α6β1. Our studies demonstrate that convection and ECM binding are the dominant mechanisms controlling EV interstitial transport and should be leveraged in nanotherapeutic design.
- Published
- 2023