Convection and extracellular matrix binding control interstitial transport of extracellular vesicles.
Convection and extracellular matrix binding control interstitial transport of extracellular vesicles.
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DOI：
10.1002/jev2.12323
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发表时间：
2023-04
影响因子：
16
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞外囊泡（EVs）影响着体内许多正常和病理生理过程。与可溶性介质相比，EV可以在其表面上运输各种蛋白质，包括细胞外基质（ECM）结合蛋白，并且它们的大尺寸（约30 - 150 nm）限制了扩散。我们从MCF 10系列（乳腺癌进展的模型人类细胞系）中分离EV，并证明随着MCF 10细胞恶性潜能的增加，EV上层粘连蛋白结合整合素α 3 β 1和α 6 β 1的存在增加。在受控的生理间隙流（0.15 - 0.75 μ m/s）下，EV在微流体装置内的运输证明对流是运输的主要机制。EV与ECM的结合增强了空间浓度和梯度，这通过阻断整联蛋白α 3 β 1和α 6 β 1来减轻。我们的研究表明，对流和ECM结合是控制EV间质转运的主要机制，应在纳米设计中加以利用。
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.
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影响因子：
16.6
作者：
Bonsergent E;Grisard E;Buchrieser J;Schwartz O;Théry C;Lavieu G
通讯作者：
Lavieu G
影响因子：
4.4
作者：
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通讯作者：
Weaver, Alissa M.
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64.5
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通讯作者：
Blalock, J. Edwin
影响因子：
11.8
作者：
Kilinc S;Paisner R;Camarda R;Gupta S;Momcilovic O;Kohnz RA;Avsaroglu B;L'Etoile ND;Perera RM;Nomura DK;Goga A
通讯作者：
Goga A
影响因子：
50.3
作者：
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通讯作者：
Lyden D