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

Abstract

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.

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

“…Moreover, HASMCs tended to be elongated on gradient RGD nanopatterns, while HUVECs tended to be fusiform. In our previous work, both SMCs and ECs exhibited weakened adhesion with the increase in RGD nanospacing on different samples (yet without a gradient of RGD nanospacing in the same sample), but the extent of descent depended upon the cell types. The actin bundles of the two cell types featured different changes with the increase in RGD nanospacing, which suggested the potential cause for different cell shapes .…”

“…In our previous work, both SMCs and ECs exhibited weakened adhesion with the increase in RGD nanospacing on different samples (yet without a gradient of RGD nanospacing in the same sample), but the extent of descent depended upon the cell types. The actin bundles of the two cell types featured different changes with the increase in RGD nanospacing, which suggested the potential cause for different cell shapes . The difference in shape might, at least partially, account for a different variation in RGD nanospacing between the leading and trailing edges of cells perceived by the two types of cells, thus influencing cell behaviors of two cell types to the gradient.…”

“…In our previous study, we found that the two types of cells had different sensitivities of cell adhesion to RGD nanospacing. 46 In the present gradient nanopatterns, we analyzed the spreading areas on both sides of the gradient region and normalized the results to that of the homogeneous nanopattern with a relatively small nanospacing, namely, region I. As shown in Figure S4, we found the sharpest decrease in the cell areas for both two cell types in the group of medium RGD nanospacings.…”

“…The cell adhesion assays and the statistic results of spreading areas of HUVECs and HASMCs indicated the weakened cell adhesion with the increase of RGD nanospacing (Figure ). In our previous study, we found that the two types of cells had different sensitivities of cell adhesion to RGD nanospacing . In the present gradient nanopatterns, we analyzed the spreading areas on both sides of the gradient region and normalized the results to that of the homogeneous nanopattern with a relatively small nanospacing, namely, region I.…”

“…Moreover, the nanoarrays were composed of hexagonally arranged Au dots with a height of about 6−7 nm as reported in our previous publication about the nanopatterns without the nanospacing gradient. 46 The size of Au dots fit with that of integrin, an adhesion receptor across the cell membrane, which enables us to control the spatial distribution of integrins by adjusting the effective nanospacing of RGD peptides linked to the Au dots.…”