Microfabricated arrays for high-throughput screening of cellular response to cyclic substrate deformation

Mechanical forces play an important role in regulating cellular function and have been shown to modulate cellular response to other factors in the cellular microenvironment. Presently, no technique exists to rapidly screen for the effects of a range of uniform mechanical forces on cellular function. In this work, we developed and characterized a novel microfabricated array capable of simultaneously applying cyclic equibiaxial substrate strains ranging in magnitude from 2 to 15% to small populations of adherent cells. The array is versatile, and capable of simultaneously generating a range of substrate strain fields and magnitudes. The design can be extended to combinatorially manipulate other mechanobiological culture parameters in the cellular microenvironment. As a first demonstration of this technology, the array was used to determine the effects of equibiaxial mechanical strain on activation of the canonical Wnt/beta-catenin signaling pathway in cardiac valve mesenchymal progenitor cells. This high-throughput approach to mechanobiological screening enabled the identification of a novel co-dependence between strain magnitude and duration of stimulation in controlling beta-catenin nuclear accumulation. More generally, this versatile platform has broad applicability in the fields of mechanobiology, tissue engineering and pathobiology.