Laterally Mobile Ligands: Cellular Response to Dynamic Surfaces

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DESCRIPTION (provided by applicant): The objective of this research is to engineer laterally mobile surface ligands that not only confer control over cell behavior but also allow cells to actively reorganize the surface with which they are interacting. Presentation of ligands on biomaterial surfaces is essential for cell adhesion and function. The manner in which ligands are presented significantly affects these processes, thereby motivating this work. The first aim is to create a ligand-surface pair that allows controlled, lateral ligand migration based on chemical recognition. This will be achieved by designing modular ligands, produced in bacteria, that contain a cell interaction domain and multiple surface binding domains. The cell interaction domain is a known binding peptide to an integrin receptor on the cell surface. The surface binding domains are peptides that bind surface anchor proteins. Independent surface attachment and detachment of multiple surface binding domains will result in lateral migration, or "walking", without the entire ligand losing contact with the surface. The second aim is to determine the effect of ligand structure on mobility. We hypothesize that features such as domain order and spacing, number and affinity of surface binding domains, and peptide display scaffolds will dictate ligand mobility. The third aim is to use this system to study cell behavior on the surface and the ability of cells to manipulate mobile ligands. Characterization of traditional cell responses to biosurfaces, adhesion, spreading, and motility, will reveal any new control over cell behavior due to mobile ligands. However, unlike traditional surfaces, cells on the mobile ligand surface will have the opportunity to actively organize or manipulate surface ligands. Tracking the ligands and corresponding cell surface receptors will provide evidence of this type of interaction. PUBLIC HEALTH RELEVANCE: The relevance of this work to public health lies in fabrication of biomaterials that control cell behavior for therapeutic or tissue engineering applications. Surfaces displaying laterally mobile ligands are a new type of biosurface that not only support cells but also promote unique interactions between cells and surfaces.