Mammalian cell morphology has been linked to the viscoelastic properties of the adhesion substrate, which is particularly relevant in biological processes such as wound repair and embryonic development where cell spreading and migration are critical. Plastic deformation, degradation, and relaxation of stress are typically coupled in biomaterial systems used to explore these effects, making it unclear which variable drives cell behavior. Here we present a nondegradable polymer architecture that specifically decouples irreversible creep from stress relaxation and modulus. We demonstrate that network plasticity 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 extracellular matrix (ECM) plasticity. Furthermore, plasticity regulates many ECM adhesion and remodeling genes. Altogether, these findings confirm 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.
Last updated on 10/15/2021
The publications shown here are the articles indexed by PubMed, not the complete list of the lab's publications.
Congrats to David and team on their recent publication in Nature Communications! Here, they utilized antigen presenting cell-mimetic scaffolds to tune CAR T-cell product functionality by controlling the precise level of stimulation during T-cell activation to accommodate individual differences in the donor cells. Check out the publication here: Enhancing CAR-T cell functionality in a patient-specific manner