Quantitative Correlation of Nanotopography with Cell Spreading via Focal Adhesions Using Adipose-Derived Stem Cells

Nanotopography mimicking extracellular environments reportedly impact cell morphological changes; however, elucidating this relationship has been challenging. To control cellular responses using nanostructures, in this study, the quantitative relationship between nanotopography and cell spreading mediated by focal adhesions (FAs) is demonstrated using adipose-derived stem cells (ASCs). The spreading of ASCs and area of FAs are analyzed for the distribution of filamentous actin and vinculin, respectively, using fluorescent images. FAs require a specific area for adhesion (herein defined as effective contact area [ECA]) to maintain cell attachment on nanopillar arrays. An ECA is the area of FAs supported by nanopillars, multiplying the area fraction (AF) of their top surface. Regarding the spreading of cells, the mean area of ASCs linearly decreases as the mean area of FAs increases. Because the area of FAs is inversely correlated to the AF of the nanopillar arrays, the spreading of cells can be quantitatively correlated with nanotopography. The results provide a conceptual framework for controlling cell behaviors to design artificial substrates for tissue-engineering applications.