Competition between cap and basal actin fiber orientation in cells subjected to contact guidance and cyclic strain

In vivo, adhesive cells continuously respond to a complex range of physical cues coming from the surrounding microenvironment by remodeling their cytoskeleton. Topographical and mechanical cues applied separately have been shown to affect the orientation of the actin stress fibers. Here we investigated the combined effects of contact guidance by topographical cues and uniaxial cyclic strain on actin cytoskeleton orientation of vascular derived cells. We devised a modular setup of stretchable circular and elliptic elastomeric microposts, capable to expose the cells to both contact guidance and uniaxial cyclic strain. A competition occurs between these cues when both contact guidance and strain are oriented along the same direction. For the first time we show that this competition originates from the distinct response of perinuclear basal and actin cap fibers: While basal fibers follow the contact guidance cue, actin cap fibers respond to the cyclic strain by strain avoidance. We also show that nuclear orientation follows actin cap fiber orientation, suggesting that actin cap fibers are responsible for cellular reorientation. Taken together, these findings may have broad implications in understanding the response of cells to combined topographical and mechanical cues.