Effects of Optimal Extracellular Matrix Plasticity on Cell Spreading and Fate

David Wang Auditorium, 3rd floor Dalia Maydan Bldg.
Dr. Joshua Micah Grolman

Dr. Joshua Micah Grolman

Wyss Institute
Harvard University

Mammalian cell morphology has been linked to the viscoplastic properties of the adhesion substrate, and this is likely of particular relevance in wound repair and embryonic development where rapid spreading, homing, and proliferation are critical. Plastic deformation, degradation, and relaxation of stress are coupled in biomaterial systems used to explore these effects, making it unclear which variable drives cell behavior. Here we present a polymer plasticizing architecture that specifically decouples irreversible creep from stress relaxation and modulus. We demonstrate that viscoplasticity independently controls mesenchymal stem cell spreading through a biphasic relationship dependent on cell-intrinsic forces, and this relationship can be shifted by inhibiting actomyosin contractility. Kinetic Monte Carlo simulations also show strong correlation with experimental cell spreading data as a function of the ECM viscoplasticity. Furthermore, plasticity regulated many ECM adhesion and remodeling genes. Altogether, these findings demonstrate a key role for matrix plasticity in stem cell biophysics, and we anticipate this will have ramifications in the design of biomaterials to enhance therapeutic applications of stem cells.