Department of Biomedical Engineering, University of California, Davis, California, USA.
Department of Pathology, University of California, San Diego, California, USA.
J Extracell Vesicles. 2023 Apr;12(4):e12323. doi: 10.1002/jev2.12323.
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.
细胞外囊泡 (EVs) 影响体内许多正常和病理生理过程。与可溶性介质相比，EVs 可以在其表面运输范围广泛的蛋白质，包括细胞外基质 (ECM) 结合蛋白，并且它们的大尺寸（约 30-150nm）限制了扩散。我们从 MCF10 系列——一种人类乳腺癌进展模型细胞系中分离出 EVs，并证明随着 MCF10 细胞恶性潜能的增加，EVs 上的层粘连蛋白结合整合素 α3β1 和 α6β1 的存在逐渐增加。在受控生理间质流（0.15-0.75μm/s）下在微流控装置内运输 EVs 表明，对流是主要的运输机制。EVs 与 ECM 的结合增强了空间浓度和梯度，而通过阻断整合素 α3β1 和 α6β1 则减轻了这种作用。我们的研究表明，对流和 ECM 结合是控制 EV 间质运输的主要机制，应在纳米治疗设计中加以利用。
