RGD Nanoarrays with Nanospacing Gradient Selectively Induce Orientation and Directed Migration of Endothelial and Smooth Muscle Cells.

Directed migration of cells through cell-surface interactions is a paramount prerequisite in biomaterial-induced tissue regeneration. However, whether and how the nanoscale spatial gradient of adhesion molecules on a material surface can induce directed migration of cells is not sufficiently known. Herein, we employed block copolymer micelle nanolithography to prepare gold nanoarrays with a nanospacing gradient, which were prepared by continuously changing the dipping velocity. Then, a self-assembly monolayer technique was applied to graft arginine-glycine-aspartate (RGD) peptides on the nanodots and poly(ethylene glycol) (PEG) on the glass background. Since RGD can trigger specific cell adhesion via conjugating with integrin (its receptor in the cell membrane) and PEG can resist protein adsorption and nonspecific cell adhesion, a nanopattern with cell-adhesion contrast and a gradient of RGD nanospacing was eventually prepared. In vitro cell behaviors were examined using endothelial cells (ECs) and smooth muscle cells (SMCs) as a demonstration. We found that SMCs exhibited significant orientation and directed migration along the nanospacing gradient, while ECs exhibited only a weak spontaneously anisotropic migration. The gradient response was also dependent upon the RGD nanospacing ranges, namely, the start and end nanospacings under a given distance and gradient. The different responses of these two cell types to the RGD nanospacing gradient provide new insights for designing cell-selective nanomaterials potentially used in cell screening, wound healing, etc.

Enlargement, Reduction, and Even Reversal of Relative Migration Speeds of Endothelial and Smooth Muscle Cells on Biomaterials Simply by Adjusting RGD Nanospacing.

Although many tissue regeneration processes after biomaterial implantation are related to migrations of multiple cell types on material surfaces, available tools to adjust relative migration speeds are very limited. Herein, we put forward a nanomaterial strategy to employ surface modification with arginine-glycine-aspartate (RGD) nanoarrays to tune in vitro cell migration using endothelial cells (ECs) and smooth muscle cells (SMCs) as demonstrated cell types. We found that migrations of both cell types exhibited a nonmonotonic trend with the increase of RGD nanospacing, yet with different peaks-74 nm for SMCs but 95 nm for ECs. The varied sensitivities afford a facile way to regulate the relative migration speeds. Although ECs migrated at a speed similar to SMCs on a non-nano surface, the migration of ECs could be controlled to be significantly faster or slower than SMCs simply by adjusting the RGD nanospacing. This study suggests a potential application of surface modification of biomaterials on a nanoscale level.