The ongoing development of prosthetic devices and implantable biomaterials will provide as yet unrealized mechanisms by which to increase the life expectancy and quality of life for many individuals. Often, however, unpredicted cellular response to implanted materials can led to immunological rejection, encapsulation of the material or hyperplasia of associated cells and cause decreased function and decreased longevity of the implanted material. Therefore, it is critical to use prosthetic materials which are compatible with appropriate physiological cell and tissue function. It is known that cellular receptors recognize relatively small peptide domains on large macromolecules and that these small peptide domains can direct cells to assume specific morphological and physiological characteristics. It is further known that many of these small peptides are found as domains within extracellular matrix components (such as laminin). This proposal is designed to make use of a powerful new technology, random combinatorial peptide libraries, to screen for and isolate previously unidentified peptide sequences that will bind cells and evoke specific physiological responses.
The specific aims of this proposal are to develop random peptide libraries; to identify peptides which react with cell receptors by means of a cell adhesion assay utilizing endothelial and neural cells; to isolate and characterize new peptides; and to begin to define the effects of these peptides on the morphology and physiology of endothelial and neuronal cells. We anticipate that this technique will not only characterize novel binding sites on known molecules, but will also identify sequences of the extracellular matrix proteins that have been associated with either cellular attachment or modulation of cellular phenotype. Coating implantable surfaces with newly elucidated structures may have significant impact on our ability to design implantable biomaterials which will elicit desirable characteristics in the prosthesis and support long term survival of the implanted material.
