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.

中文翻译：

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基质力学和水渗透调节细胞外囊泡运输。

细胞释放细胞外囊泡 (EV) 进行长距离通信，这需要 EV 穿越细胞外基质 (ECM)。然而，鉴于 EV 的尺寸通常大于 ECM 的网格尺寸，尚不清楚它们如何通过密集的 ECM。在这里，我们表明，与合成纳米颗粒相比，电动汽车很容易通过纳米多孔 ECM 运输。使用工程水凝胶，我们证明了基质的机械性能在限制条件下调节异常 EV 传输。基质应力松弛允许电动汽车克服限制，较高的交联密度有助于通过聚合物网格的波动传输运动，从而导致自由扩散和快速传输。此外，通过 aquaporin-1 的水渗透介导了 EV 的可变形性，这进一步支持了 EV 在水凝胶和脱细胞基质中的运输。我们的结果为受限环境中电动汽车运输的性质提供了证据，并证明了对基质力学和水渗透的意外依赖性。