This proposal takes a biomimetic approach to understanding how biomaterial composition and structure relate to the mechanical and integrin binding site environment experienced by contacted cells and then varies these parameters to elicit desired cell behaviors. Since basement membranes have wide relevance in the body (e.g., as a substrate for gingival epithelial cells), biomimetic basement membranes will be developed. The hypothesis that the elastic modulus of two-component collagen IV/laminin materials can be predicted from their molecular composition using the cellular solids model and visco-elastic theory and that their cell adhesion strength can be predicted from molecular composition through calculating the number of integrin bonds will be tested. A second hypothesis that it is possible to vary the membrane elastic modulus while holding the integrin bond number constant and vice versa, by variation of the laminin/collagen IV composition of the membrane, will also be tested.
The Specific Aims are to assemble and characterize single-component membranes of collagen IV or laminin, assemble and characterize two-component membranes by co-assembling collagen IV and laminin, and finally systematically vary the mechanical modulus and integrin binding site density to achieve differences in cell migration behavior. Potential applications range from coatings for dental implants to artificial vascular grafts. In particular for dental applications, a bioactive material would be able to strengthen binding of the epithelial lining of the gingiva to the implant in order to exclude bacteria from the subepithelial gingival tissue. The candidate, having completed a PhD in the laboratories of Dr. Douglas Lauffenburger and Dr. Roger Kamm at MIT, has developed expertise in the field of self-assembling biomaterials that have potential use in medical implants. Current post-doctoral research in the laboratory of Dr. Harold Erickson at Duke University extends the candidate's knowledge into the self-assembly of naturally occurring extracellular matrix proteins. Having accepted a position as Assistant Professor at Arizona State University, the candidate's immediate goal is to lay a strong foundation for the learning environment and productivity of his laboratory. In the long term, this research will synergistically combine the candidate's expertise in the rational design of biomaterials and extracellular matrix self-assembly to produce bioactive materials.
