Modulation of endothelial cell migration via manipulation of adhesion site growth using nanopatterned surfaces.
Modulation of endothelial cell migration via manipulation of adhesion site growth using nanopatterned surfaces.
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DOI：
10.1021/am508906f
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发表时间：
2015-02
影响因子：
9.5
通讯作者：
J. H. Slater;P. J. Boyce;Matthew P Jancaitis;Harold E Gaubert;A.-L. Chang;M. Markey;W. Frey
中科院分区：
文献类型：
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作者：
J. H. Slater;P. J. Boyce;Matthew P Jancaitis;Harold E Gaubert;A.-L. Chang;M. Markey;W. Frey
采用呈现 92 至 405 nm 离散纤连蛋白域的正交功能化纳米图案表面来研究限制粘附位点生长对细胞迁移的影响。我们证明，使用亚 100 nm 模式将粘附位点的生长限制为小的、未成熟的粘附，会诱导细胞形成数量显着增加的更小、更密集的粘附，这些粘附与肌动蛋白应力纤维几乎没有相互作用。表现出这些特征的人脐静脉内皮细胞在扩散方面表现出高度动态的波动，与非图案对照细胞相比，速度增加了 4.8 倍。当在更大的纳米图案（222 至 405 nm）上培养的细胞中，粘附的尺寸逐渐成熟时，扩散面积和迁移的动态波动开始减慢，但与对照组相比，细胞的速度仍然增加了 2.1 倍。由于使用非图案化对照解除了对粘附位点生长的所有限制，细胞形成的数量显着减少、密度降低、更大、成熟的粘附，作为肌动蛋白应力纤维的终止位点，并且迁移速度显着减慢。结果显示，随着粘附位点大小的增加，细胞速度呈指数衰减，表明防止大的成熟粘附的形成可能会破坏细胞稳定性，从而诱导高度迁移行为。
Orthogonally functionalized nanopatterend surfaces presenting discrete domains of fibronectin ranging from 92 to 405 nm were implemented to investigate the influence of limiting adhesion site growth on cell migration. We demonstrate that limiting adhesion site growth to small, immature adhesions using sub-100 nm patterns induced cells to form a significantly increased number of smaller, more densely packed adhesions that displayed few interactions with actin stress fibers. Human umbilical vein endothelial cells exhibiting these traits displayed highly dynamic fluctuations in spreading and a 4.8-fold increase in speed compared to cells on nonpatterned controls. As adhesions were allowed to mature in size in cells cultured on larger nanopatterns, 222 to 405 nm, the dynamic fluctuations in spread area and migration began to slow, yet cells still displayed a 2.1-fold increase in speed compared to controls. As all restrictions on adhesion site growth were lifted using nonpatterned controls, cells formed significantly fewer, less densely packed, larger, mature adhesions that acted as terminating sites for actin stress fibers and significantly slower migration. The results revealed an exponential decay in cell speed with increased adhesion site size, indicating that preventing the formation of large mature adhesions may disrupt cell stability thereby inducing highly migratory behavior.