Nanoparticle-Functionalized Polymer Platform for Controlling Metastatic Cancer Cell Adhesion, Shape, and Motility

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 similar to 140 particles per 400 mu m(2) (similar to 1.7 mu m 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 En-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.