Coordinated extracellular matrix spatiotemporal reorganization helps
regulate cellular differentiation, maturation, and function in
vivo, and is therefore vital for the correct formation,
maintenance, and healing of complex anatomic structures. In order to evaluate
the potential for cultured cells to respond to dynamic changes in their
in vitro microenvironment, as they do in
vivo, the collective behavior of primary cardiac muscle cells
cultured on nanofabricated substrates with controllable anisotropic topographies
was studied. A thermally induced shape memory polymer (SMP) was employed to
assess the effects of a 90° transition in substrate pattern orientation
on the contractile direction and structural organization of cardiomyocyte
sheets. Cardiomyocyte sheets cultured on SMPs exhibited anisotropic contractions
before shape transition. 48 hours after heat-induced shape transition, the
direction of cardiomyocyte contraction reoriented significantly and exhibited a
bimodal distribution, with peaks at ~ 45 and −45 degrees (P
< 0.001). Immunocytochemical analysis highlighted the significant
structural changes that the cells underwent in response to the shift in
underlying topography. The presented results demonstrate that initial
anisotropic nanotopographic cues do not permanently determine the organizational
fate or contractile properties of cardiomyocytes in culture. Given the
importance of surface cues in regulating primary and stem cell development,
investigation of such tunable nanotopographies may have important implications
for advancing cellular maturation and performance in vitro, as
well as improving our understanding of cellular development in response to
dynamic biophysical cues.