Department of Pharmacology and Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.
Nat Nanotechnol. 2020 Mar;15(3):217-223. doi: 10.1038/s41565-020-0636-2. Epub 2020 Feb 17.
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.
细胞通过释放细胞外囊泡 (EVs) 进行长距离通讯，这需要 EVs 穿越细胞外基质 (ECM)。然而，鉴于 EVs 的大小通常大于 ECM 的网格尺寸，因此不清楚它们如何能够穿越致密的 ECM。在这里，我们表明，与合成纳米颗粒相比，EVs 很容易通过纳米多孔 ECM 进行运输。使用工程化水凝胶，我们证明了基质的机械性质调节了受限条件下异常的 EV 运输。基质应力松弛使 EV 能够克服限制，并且更高的交联密度有利于通过聚合物网格进行波动的运输运动，从而导致自由扩散和快速运输。此外，水通过水通道蛋白-1 的渗透介导了 EV 的变形性，这进一步支持了 EV 在水凝胶和去细胞基质中的运输。我们的结果为 EV 在受限环境中的运输性质提供了证据，并证明了对基质力学和水渗透的意外依赖性。
