(271f) Solid Surface Tension of Biomaterials Direct Cellular Behaviors through Integrins

Cells physically interrogate their extracellular environment to make decisions related to cell proliferation, differentiation, migration and other critical processes. In addition to biochemical properties, physical properties of the extracellular matrix, including its stiffness, are key regulators for cell behaviors. Typically, on stiff substrates, cells display large spreading areas, assemble robust integrin-based adhesion complexes, whereas on soft substrates these functions are suppressed. However, cell behaviors that defy expectations based on substrate rigidity alone have been observed.
Recent studies have illustrated that solid surface tension can have a dominant role in the mechanical behaviors of soft materials with vanishingly small elasticity. A central hypothesis underlying our proposed work is that surface tension can override directives from elasticity in controlling cell response. We have now demonstrated that cells interacting with soft materials with appreciable surface tension primarily sense and respond to surface tension and not the bulk elastic moduli of the materials. Our results are consistent with theory that predicts that solid surface tension can dominate over elasticity at cellular length scales. Even on very soft substrates (E=100 Pa), if the surface tension is appreciable, cells assemble robust adhesion complexes and cytoskeleton stress fibers, spread over large areas, upregulate canonical integrin-based signal transduction, proliferate and migrate efficiently. Remarkably, we find that cells can even spread and migrate on liquid biomaterials that have high surface tension. On these materials, cells migrate through a highly collective, swarming-type motility that is significantly faster than migration on solid biomaterials. Together, our results indicate that material surface tension is important criteria for the design of biomaterials for cell growth and morphogenesis in tissue engineering.