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Tailored Surfaces for Exploring the Stem Cell Microenvironment Kristopher A. Kilian University of Chicago, Department of Chemistry and Howard Hughes Medical Institute Mesenchymal stem cells (MSCs) are multipotent cells that reside in the perivascular space and are involved in the maintenance of cartilage, bone, fat and potentially other tissues. Here I present the use of substrates that mimic the extracellular matrix to explore the cues in the cellular microenvironment that direct MSC fate. First, I will show how micropatterned self‐assembled monolayers of alkanethiolates on gold can be used to influence differentiation by modulating the shape of single cells. Geometries that promote a contractile cytoskeleton promote osteogenesis while geometries that promote a less organized cytoskeleton promote adipogenesis. Next I will show how paracrine signaling between adjacent micropatterned cells feeds into mechanotransduction pathways and how varying the pattern density can influence the differentiation outcome. Finally, I will present evidence that MSC fate can be guided solely by the affinity and density of ligand‐receptor interactions at a surface. Cells adherent to monolayers that present the high affinity cyclic‐RGD peptide show increased osteogenesis marker expression across a range of ligand densities. In contrast, cells on monolayers presenting the lower affinity linear‐RGD peptide express early markers of myogenesis at high density and neurogenesis at low density of ligand. Taken together, these studies demonstrate how functionalized monolayer surfaces can be used to explore the interplay of physical, chemical and biological signaling during stem cell differentiation.
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