A Balance of Substrate Mechanics and Matrix Chemistry Regulates Endothelial Cell Network Assembly
A Balance of Substrate Mechanics and Matrix Chemistry Regulates Endothelial Cell Network Assembly
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DOI：
10.1007/s12195-008-0022-x
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发表时间：
2008-09-01
影响因子：
2.8
通讯作者：
Reinhart-King, Cynthia A.
中科院分区：
文献类型：
--
作者：
Califano, Joseph P.;Reinhart-King, Cynthia A.
在特定的细胞外基质信号的驱动下，内皮细胞可以自发地组装成网络。细胞网络组装在一定程度上由底物硬度和细胞外基质化学共同决定；然而，促进细胞网络组装的底物力学和基质化学之间的平衡还没有被很好地理解。由于力学和化学都可以改变细胞-底物和细胞-细胞黏附，我们假设细胞网络组装可以在使细胞-底物黏附最小化的底物上促进，同时促进细胞-细胞连接。为了验证这些假说，将牛主动脉内皮细胞(BAEC)种植在用I型胶原衍生的可变顺应性聚丙烯酰胺(PA)底物上，并随时间观察。我们的结果表明，细胞网络组装可以在足够柔顺的底物上(杨氏模数，E=200pa)和较硬的底物(E=10,000 pA)但粘连配体较少的底物上诱导。在这两种情况下，细胞底物粘附性都会降低，这可能会增强细胞的粘附性。此外，我们的数据表明，纤维连接蛋白聚合稳定了细胞间的接触，并且无论底物顺应性或底物结合配体的密度如何，网络的形成都是必要的。这些数据证明了在指导细胞网络组装时底物力学和化学之间的平衡。
Driven by specific extracellular matrix cues, endothelial cells can spontaneously assemble into networks. Cell network assembly is, in part, dictated by both substrate stiffness and extracellular matrix chemistry; however, the balance between substrate mechanics and matrix chemistry in promoting cell network assembly is not well understood. Because both mechanics and chemistry can alter cell-substrate and cell-cell adhesion, we hypothesized that cell network assembly can be promoted on substrates that minimize cell-substrate adhesivity while promoting cell-cell connections. To investigate these hypotheses, bovine aortic endothelial cells (BAEC) were seeded on variably compliant polyacrylamide (PA) substrates derivatized with type I collagen and observed over time. Our results indicate that cell network assembly can be induced on substrates that are sufficiently compliant (Young's modulus, E = 200 Pa) and present significant amounts of substrate-bound ligand, and on substrates that are stiffer (E = 10,000 Pa) but which present less adhesive ligand. In both of these cases, cell substrate adhesivity is decreased, which may enhance cell cell adhesivity. Moreover, our data indicate that fibronectin polymerization stabilizes cell-cell contacts and is necessary for network formation to occur regardless of substrate compliance or the density of substrate-bound ligand. These data demonstrate the balance between substrate mechanics and chemistry in directing cell network assembly.