Nanotopographic Control of Cytoskeletal Organization

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Abstract
Growth of 3T3-L1 preadipocytes on a nanoscalar poly(ethylene terephthalate) (PET) surface produced an absence of the intracellular stress fibers characteristic of cell growth on “normal” planar surfaces. This phenomenon was consistently observed from time zero throughout 3 days of culture and was accompanied by changes in paxillin expression along with an approximately 50% decrease in the number of adherent cells in response to 500 dynes/cm2 of shear stress. This suggests that the cytoskeleton in cells adherent to nanofibrillar surfaces does indeed form, but at a smaller, more difficult to observe scale. We propose a novel mechanism by which the growth and clustering of integrin-associated focal adhesions on surface nanofibrils regulates cytoskeletal development. The width of the extracellular matrix contacts is constrained by the width of the nanofibrils and the absence of any surface between them. The limited dimensions of these point contacts then constrain receptor polymerization and the associated aggregation of actin filaments. The existence of a topographic mechanism leading to growth-limited integrin clustering is hypothesized.