Open AccessMatrix mechanics and water permeation regulate extracellular vesicle transport
Author(s) -
Stephen Lenzini,
Raymond Bargi,
Gina G. Chung,
JaeWon Shin
Publication year - 2020
Publication title -
nature nanotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 14.308
H-Index - 353
eISSN - 1748-3395
pISSN - 1748-3387
DOI - 10.1038/s41565-020-0636-2
Subject(s) - self healing hydrogels , permeation , extracellular matrix , decellularization , nanotechnology , matrix (chemical analysis) , biophysics , materials science , vesicle , vesicular transport protein , water transport , nanoporous , membrane , chemistry , composite material , polymer chemistry , biochemistry , biology , water flow , environmental engineering , engineering
Cells release extracellular vesicles (EVs) to communicate over long distances, which requires EVs to traverse the extracellular matrix (ECM). However, given that the size of EVs is usually larger than the mesh size of the ECM, it is not clear how they can travel through the dense ECM. Here we show that, in contrast to synthetic nanoparticles, EVs readily transport through nanoporous ECM. Using engineered hydrogels, we demonstrate that the mechanical properties of the matrix regulate anomalous EV transport under confinement. Matrix stress relaxation allows EVs to overcome the confinement, and a higher crosslinking density facilitates a fluctuating transport motion through the polymer mesh, which leads to free diffusion and fast transport. Furthermore, water permeation through aquaporin-1 mediates the EV deformability, which further supports EV transport in hydrogels and a decellularized matrix. Our results provide evidence for the nature of EV transport within confined environments and demonstrate an unexpected dependence on matrix mechanics and water permeation.