Schwann cell behavior in three-dimensional collagen gels: Evidence for differential mechano-transduction and the influence of TGF-beta 1 in morphological polarization and differentiation

Schwann cells (SCs) cultured on and within magnetically aligned collagen gels were examined for their abilities to spread and exhibit contact guidance, two functions that are relevant to their potential enhancement of neurite migration and regeneration in entubulation repair of transection-type nerve injuries. Cells seeded at or near the surfaces of gels abandoned their initially spherical shapes, adopting spread morphologies rapidly compared to cells within the gels. Those few cells within the gels that did spread exhibited marked contact guidance responses, aligning strongly with the aligned collagen fibrils. Spreading of cells in gels could not be induced by varied cell concentration, collagen density, mitogen presence, inclusion of soluble laminin, or use of fibrin gel in lieu of collagen. However, cells that settled at the interface between collagen gel layers during gellation of the top layer above a preformed bottom layer were highly spread. This suggests that a differential mechanical interaction across the cell at an interface, where at least one surface presents constituents of the basal lamina, permits the Schwann cell to rapidly revert to a spread, differentiated phenotype. Unlike other reagents, TGF-β1 was able to induce significant SC spreading as early as 4 h post-seeding. Consistent with the differential-mechanical cue mechanism, TGF-β1 appears to facilitate this response, at least in part, by upregulating β1 integrin expression, thereby enabling the SC to more acutely detect these local cues in the mechanical environment.