Role of Cell-Mediated Enzymatic Degradation and Cytoskeletal Tension on Dynamic Changes in the Rheology of the Pericellular Region Prior to Human Mesenchymal Stem Cell Motility

Human mesenchymal stem cells (hMSCs) are encapsulated in synthetic matrix metalloproteinase (MMP) degradable poly(ethylene glycol)-peptide hydrogels to characterize cell-mediated degradation of the pericellular region using multiple particle tracking microrheology. The hydrogel scaffold is degraded by cell-secreted enzymes and cytoskeletal tension. We determine that cell-secreted enzymatic degradation is the main contributor to changes in the pericellular region, with cytoskeletal tension playing a minimal role. Measured degradation profiles for untreated and myosin II inhibited hMSCs have the highest cross-link density around the cell. We hypothesize that cells are also secreting tissue inhibitor of metalloproteinases (TIMPs) to inhibit MMPs, which allow cell spreading and attachment prior to motility. We develop a Michaelis Menten competitive enzymatic inhibition model which accurately describes the degradation profile due to MMP-TIMP unbinding.