Growth behavior of fibroblasts on microgrooved polystyrene

Epithelial contact guidance on well-defined micro- and nanostructured substrates

“…There are no previous reports on the orientation of focal adhesions in epithelial cells cultured on topographically patterned substrates. Focal adhesion and microfilament alignment was observed in fibroblasts and macrophages aligned along micrometer-sized grooves and ridges (Britland et al, 1996;den Braber et al, 1998;Matsuzaka et al, 2000;Meyle et al, 1994;Walboomers et al, 1998) and was proposed to be the driving force for the observed contact guidance. The generation of tension by actin stress fibers is known to be necessary for the formation of focal adhesions (ChrzanowskaWodnicka and .…”

“…On grooves with nanoscale depths, cell alignment also correlated with groove depth, for both nanoscale (Clark et al, 1991) and micrometer-scale lateral feature dimensions (Wojciak-Stothard et al, 1996). Cells have been found increasingly able to descend into the grooves and form focal adhesions on the floor of the grooves as the ridge width was increased and the groove depth decreased (Walboomers et al, 1998;Walboomers et al, 1999a). On 1 µm or 2 µm wide grooves, cells have rarely been reported to protrude into the grooves (Walboomers et al, 1999a) and therefore most adhesions were observed to occur on the ridge (Matsuzaka et al, 2000;Meyle et al, 1994;van Kooten and von Recum, 1999).…”

“…Focal adhesions are adhesive structures containing aggregates of transmembrane proteins called integrins that link the actin cytoskeleton to extracellular matrix proteins. Focal adhesions and actin microfilament bundles (Britland et al, 1996;den Braber et al, 1998;Matsuzaka et al, 2000;Meyle et al, 1994;Walboomers et al, 1998) and microtubules (Oakley and Brunette, 1995a;Oakley et al, 1997) have all been found to align along micrometer-sized grooves and ridges, in cells aligned along these topographic features. On smooth substrates, cells and cytoskeletal elements did not display any preferred orientations.…”

“…According to this hypothesis, the topographic discontinuities have different surface energy and act as sites of preferred protein deposition, creating patterns of proteins along the topographic patterns. Walboomers and colleagues have not found a preference for focal adhesion formation along the groove/ridge boundaries (Walboomers et al, 1998), suggesting that adhesive proteins do not colocalize preferentially with the surface discontinuities. Furthermore, cells have been shown to exhibit contact guidance when cultured on anisotropic substrates without sharp discontinuities (Walboomers et al, 1999a).…”

“…Oblong focal adhesions 1-10 µm long (Riveline et al, 2001) orient along the direction of the ridges to maximize their contact area, leading to an alignment of microfilament bundles and of the cell body as a whole (den Braber et al, 1996b;den Braber et al, 1998;Meyle et al, 1994). This explanation has been questioned on the basis of observations that focal adhesions can bend around groove/ridge boundaries (Walboomers et al, 1998).…”