Contractility-dependent modulation of cell proliferation and adhesion by microscale topographical cues.
Engineering of cellular assembly on biomaterial scaffolds by utilizing microscale topographical cues has emerged as a powerful strategy in cardiovascular tissue engineering and regenerative medicine. However, the mechanisms through which these cues are processed to yield changes in canonical cell behaviors remain unclear. Previously, we showed that when mixtures of cardiomyocytes and fibroblasts were cultured on polydimethylsiloxane surfaces studded with microscale pillars (micropegs), fibroblast proliferation was dramatically suppressed, which suggests that the micropegs could be exploited to minimize fibrosis and scar formation. Here, we demonstrate that this effect relies on altered adhesive and micromechanical interactions between individual cells and micropegs. First, we show that the proliferation of a cell physically attached to a micropeg is significantly lower than that of a cell cultured on a featureless region of the substrate. Micropeg adhesion is accompanied by a marked elongation in cell and nuclear shape. When fibroblast contractility is pharmacologically attenuated through low-dose inhibition of either Rho-associated kinase or myosin light chain kinase, the potency with which micropeg adhesion suppresses cell proliferation is significantly reduced. Together, our results support a model in which cell fate decisions may be directly manipulated within tissue engineering scaffolds by the inclusion of microtopographical structures that alter cellular mechanics.
Thakar
Rahul G
RG
Department of Physiology, University of California, San Francisco 203C Byers Hall Box 2520, 1700 4th Street San Francisco, CA 94158-2330, USA.
Chown
Matthew G
MG
Patel
Anuj
A
Peng
Lily
L
Kumar
Sanjay
S
Desai
Tejal A
TA
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002467:Cell Nucleus; D049109:Cell Proliferation; D003599:Cytoskeleton; D005347:Fibroblasts; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D049329:Nanostructures / Q000648:ultrastructure; D054460:rho-Associated Kinases / Q000378:metabolism
D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase