Figure 6.
Nanotopography downregulates epidermal tight junctions via integrin activation and myosin light chain phosphorylation. Proposed mechanism for nanotopography-mediated enhancement of transdermal drug delivery: Integrins bind to adsorbed proteins on the nanotopography and induce downstream clustering of focal adhesion proteins such as pFAK and vinculin. Formation of focal adhesions, in turn, leads to phosphorylation of myosin light chain and increased myosin contraction of the actin cytoskeleton. Actin dynamics ultimately remodel and downregulate proteins at the epidermal tight junction, thereby allowing increased paracellular transport within the epidermis. By contrast, we propose that the lack of topography on the flat surfaces fails to induce integrin clustering and the downstream initiation of focal adhesions and actomyosin activation (right lower image).