Engineering Cell Fate By Controlling Cell-Matrix Interactions on Geometrically Defined Peptide Surfaces

The architecture of the stem cell microenvironment provides physical, chemical and biological cues to guide cell fate and orchestrate tissue form and function. Substrates that are designed to emulate this architecture are useful tools for exploring the biophysical basis for cell fate determination. In this presentation I will discuss our efforts in modifying both “hard” and “soft” biomaterials with patterned biomolecules to study stem cell fate decisions. First, I will demonstrate how soft lithography can be used to pattern peptides to functionalized self-assembled monolayers on gold for exploring signaling in single mesenchymal stromal cells. Adhesion to a high affinity cyclic RGD peptide surface leads to enhanced expression of smooth muscle markers compared to surface presenting the linear peptide. Increasing the aspect ratio of the single cells using microcontact printing shows a further enhancement in expression of smooth muscle markers which suggests that cell shape and integrin mediated cell adhesion both contribute independently to the smooth muscle phenotype. Next I will show how this platform can serve to identify optimal 2D microenvironments for translation to hydrogel substrates. Micropatterning stem cells on beaded polyacrylamide gels demonstrates how both shape and the composition of adhesion ligand will direct traction force and the differentiation outcome. Taken together, these studies reveal how a well-defined presentation of signaling ligands at the cell-biomaterial interface is critical for studying and ultimately controlling cell fate decisions.