The objective of this research is to engineer laterally mobile surface ligands that not only confer control overcell 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 inwhich ligands are presented significantly affects these processes, thereby motivating this work.
The first aimi s to create a ligand-surface pair that allows controlled, lateral ligand migration based on chemicalrecognition. This will be achieved by designing modular ligands, produced in bacteria, that contain multiplesurface binding domains and cell interaction domains. The cell interaction domain is a known bindingpeptide to an integrin receptor on the cell surface. The surface binding domains are coiled-coil motifs orspecific binding peptides that interact surface anchor proteins. Independent surface attachment anddetachment of multiple surface binding domains will result in lateral migration, or 'walking', without the entireligand losing contact with the surface.
The second aim i s to determine the effect of ligand structure onmobility. We hypothesize that features such as domain order and spacing, number and affinity of surfacebinding domains, and peptide display scaffolds will dictate ligand mobility.
The third aim i s to use this systemto study cell behavior on the surface and the ability of cells to manipulate mobile ligands. Characterization oftraditional cell responses to biosurfaces, proliferation, adhesion, spreading, motility, and differentiation willreveal any new control over cell behavior due to mobile ligands. However, unlike traditional surfaces, cellson the mobile ligand surface will have the opportunity to actively organize or manipulate surface ligands.Simultaneous single molecule tracking of the ligands and corresponding cell integrins will provide evidenceof this type of interaction. With novel cell interactions, mobile ligand surfaces will have therapeutic benefit astissue engineering scaffolds, wound healing materials, or cell differentiation platforms.The relevance of this work to public health lies in fabrication of biomaterials that control cell behavior fortherapeutic or tissue engineering applications. Surfaces displaying laterally mobile ligands are a new type ofbiosurface that not only support cells but also promote unique interactions between cells and surfaces. Thistype of material can serve as a structure on which to grow new tissue or assist in repair of damaged ordiseased tissue.
