Abstract
Strain stiffening of extracellular matrices is increasingly recognized as a mechanical mechanism to tune cell behaviors and maintain tissue functions. Routinely, the mechanical properties of a matrix are determined using shear rheology in the absence of cells. However, this method lacks the cell-induced stiffening and consistently underestimate the (macroscopic) stiffness of biogels. We introduce a method using shear rheology in combination with cells and synthetic matrices, polyisocyanide hydrogels that possess nonlinear mechanics. Human adipose-derived stem cells (hASCs) were encapsulated in gels from polymers with different contour lengths but a constant peptide density and polymer concentration to study the cell-mediated nonlinear mechanical change of ECM quantitatively. Other parameters such as cell line, cell density, type of cell adhesion peptides were also changed systematically. Rheology results reveal that cells can adjust matrix stiffness to a similar value via contraction regardless of the cell-free elasticity of gels. Fluorescence imaging further shows the local physical matrix remodeling by cells. Our results suggest that biogels or their mimics with nonlinear mechanics possess dynamic mechanical properties that are highly responsive to cellular intervention. Our approach offers a new platform with synthetic semi-flexible polymer networks for research on the cell-matrix interface.
