Engineering Dynamic Cell-Material Interfaces to decode How Cells Communicate with Their Environment

The extracellular matrix (ECM) is a complex physical network composed of multiple molecular constituents (proteins, proteoglycans, growth factors) that collectively regulate biological behavior in a highly dynamic interplay with cells. A major challenge in matrix biology is to understand how ECM dynamics may contribute to cell fate. To meet this challenge, there is a need for scaffolds whose properties change temporally in a predictable, programmable, or even responsive manner and enable the dynamic display of cues to cells. I will discuss the development of DNA/peptide-based stimuli-responsive interfaces as in vitro model systems able to recapitulate the dynamic cell-matrix interface. I will demonstrate how we utilize our innovative biomimetic platform for the temporal display of integrin-engaging cell-adhesive signals. Transient display of αVβ3-selective ligands instructed fibroblast cells to reversibly spread and contract in response to changes in ligand exposure over multiple cycles, exhibiting a universal kinetic response. Also, cells that were triggered to spread and contract repeatedly exhibited greater enrichment of integrins in focal adhesions versus cells cultured on persistent ligand-displaying surfaces. This dynamic platform will allow us to uncover the molecular code by which cells sense and respond to changes in their environment and will provide insights into ways to program cellular behavior.