Guiding hMSC Adhesion and Differentiation on Supported Lipid Bilayers

Mesenchymal stem cells (MSCs) are intensively investigated for regenerative medicine applications due to their ease of isolation and multilineage differentiation capacity. Hence, designing instructive microenvironments to guide MSC behavior is important for the generation of smart interfaces to enhance biomaterial performance in guiding desired tissue formation. Supported lipid bilayers (SLBs) as cell membrane mimetics can be employed as biological interfaces with easily tunable characteristics such as biospecificity, mobility, and density of predesigned ligand molecules. Arg-Gly-Asp (RGD) ligand functionalized SLBs are explored for guiding human MSC (hMSC) adhesion and differentiation by studying the effect of changes in ligand density and mobility. Cellular and molecular analyses show that adhesion occurs through specific interactions with RGD ligands where the extent is positively correlated to changes in ligand density. Furthermore, cell area is significantly regulated by ligand density on ligand-mobile SLBs when compared to ligand-immobile SLBs. Finally, the osteogenic differentiation capacity of hMSCs is positively correlated to ligand density on ligand-mobile SLBs indicating that regulation of cell spreading is linked to cell differentiation capacity. These results demonstrate that hMSC behavior can be directed on SLBs by molecular design and presents SLBs as versatile platforms for future engineering of smart biomaterial coatings.