(806g) The Dynamic Interplay Between Cell and Substrate Mechanical Properties

The engineering of polymer surfaces or matrices that are capable of controlling cell adhesion has been widely explored. In nearly all of these works, the polymer chains (and ligands) are chemically attached to the underlying substrate, and therefore these systems are inherently static. By contrast, cellular environments such as the extracellular matrix are dynamic and remodeled by biochemical reactions and biophysical forces. Borrowing this concept from Nature, we created polymer films by an interfacial self-assembly process, whereby individual (ligand-modified) chains exhibit lateral mobility. Furthermore, we can simultaneously tune the viscoelastic properties of the films. NIH 3T3 fibroblasts seeded on these films exhibit biphasic responses in spreading and adhesion strength as a function of ligand lateral mobility, with a minimal response for intermediate mobility values. These results establish that ligand mobility is a significant, but thus far overlooked, factor in material-induced cell responses. At the same time, cell spreading showed a weak decreasing response against the film storage modulus, which is in contrast to prior works using densely crosslinked hydrogel networks. We believe that these different trends reflect differences in molecular properties (lateral mobility) and continuum properties (storage and loss moduli), but must also consider cellular feedback response caused by the material itself. To investigate material-induced changes in cell behavior, we are currently exploring the effects of blocking either avb3 or a5b1 integrins and the consequences on cell spreading and focal adhesion (FA) dynamics. We are also studying cell mechanical properties by pharmacologically-induced de-adhesion assays. Previous works have shown a good correlation between de-adhesion and the viscoelastic properties of cells. Our work introduces the fabrication of novel materials whose physical properties more closely represent the dynamic interaction between cells and their extracellular environment. Combined characterization of both molecular and continuum properties, of both cells and their substrates, will give new insight as to how cells sense and respond to their ever-changing surroundings.