Department of Chemistry, Seoul National University, Seoul, 151-747, Korea.
ACS Nano. 2011 Jul 26;5(7):5444-56. doi: 10.1021/nn202103z. Epub 2011 Jun 29.
Controlling and understanding the changes in metastatic cancer cell adhesion, shape, and motility are of paramount importance in cancer research, diagnosis, and treatment. Here, we used gold nanoparticles (AuNPs) as nanotopological structures and protein nanocluster forming substrates. Cell adhesion controlling proteins [in this case, fibronection (Fn) and ephrinB3] were modified to AuNPs, and these particles were then modified to the layer-by-layer (LbL) polymer surface that offers a handle for tuning surface charge and mechanical property of a cell-interfacing substrate. We found that metastatic cancer cell adhesion is affected by nanoparticle density on a surface, and ∼140 particles per 400 μm(2) (∼1.7 μm spacing between AuNPs) is optimal for effective metastatic cell adhesion. It was also shown that the AuNP surface density and protein nanoclustering on a spherical AuNP are controlling factors for the efficient interfacing and signaling of metastatic cancer cells. Importantly, the existence of nanotopological features (AuNPs in this case) is much more critical in inducing more dramatic changes in metastatic cell adhesion, protrusion, polarity, and motility than the presence of a cell adhesion protein, Fn, on the surface. Moreover, cell focal adhesion and motility-related paxillin clusters were heavily formed in cell lamellipodia and filopodia and high expression of phospho-paxillins were observed when the cells were cultured on either an AuNP or Fn-modified AuNP polymer surface. The ephrin signaling that results in the decreased expression of paxillin was found to be more effective when ephrins were modified to the AuNP surface than when ephrinB3 was directly attached to the polymer film. The overall trend for cell motility change is such that a nanoparticle-modified LbL surface induces higher cell motility and the AuNP modification to the LbL surface results in more pronounced change in cell motility than Fn or ephrin modification to the LbL surface.
控制和理解转移性癌细胞黏附、形态和运动的变化，在癌症研究、诊断和治疗中至关重要。在这里，我们使用金纳米粒子（AuNPs）作为纳米拓扑结构和蛋白质纳米簇形成的基底。细胞黏附控制蛋白（在这种情况下是纤维连接蛋白（Fn）和 EphrinB3）被修饰到 AuNPs 上，然后这些颗粒被修饰到层层（LbL）聚合物表面，该表面为调节细胞界面基底的表面电荷和机械性能提供了一种手段。我们发现，癌细胞黏附受表面上纳米颗粒密度的影响，并且表面上大约 140 个纳米颗粒/400 μm²（AuNPs 之间的间隔约为 1.7 μm）对于有效黏附转移性细胞是最佳的。还表明，AuNP 表面密度和球形 AuNP 上的蛋白质纳米簇是控制转移性癌细胞有效界面相互作用和信号转导的因素。重要的是，与表面上存在细胞黏附蛋白 Fn 相比，纳米拓扑特征（在这种情况下是 AuNPs）的存在更能引起转移性细胞黏附、突起、极性和运动的更显著变化。此外，当细胞在 AuNP 或 Fn 修饰的 AuNP 聚合物表面上培养时，细胞斑蝥和丝状伪足中形成了大量的细胞黏附斑和运动相关的桩蛋白簇，并且观察到磷酸化桩蛋白的高表达。当 Ephrins 修饰到 AuNP 表面时，而不是 EphrinB3 直接附着在聚合物膜上时，Ephrin 信号导致的 paxillin 表达减少更为有效。细胞运动变化的总体趋势是，纳米颗粒修饰的 LbL 表面诱导更高的细胞运动，并且 AuNP 修饰到 LbL 表面导致比 Fn 或 Ephrin 修饰到 LbL 表面更明显的细胞运动变化。
