PROTEINLIKE MOLECULAR ARCHITECTURE - BIOMATERIAL APPLICATIONS FOR INDUCING CELLULAR RECEPTOR-BINDING AND SIGNAL-TRANSDUCTION

The development of biomaterials with desirable biocompatibility has pr esented a difficult challenge for tissue engineering researchers. Firs t and foremost, materials themselves tend to be hydrophobic and/or thr ombogenic in nature, and face compatibility problems upon implantation . To mediate this problem, researchers have attempted to graft protein s or protein fragments onto biomaterial surfaces to promote endothelia l cell attachment and minimize thrombosis. We envisioned a novel appro ach, based on the capability of biomolecules to self-assemble into wel l-defined and intricate structures, for creating biomimetic biomateria ls that promote cell adhesion and proliferation. One of the most intri guing self-assembly processes is the folding of peptide chains into na tive protein structures. We have developed a method for building prote inlike structural motifs that incorporate sequences of biological inte rest. A lipophilic moiety is attached onto an N-alpha-amino group of a peptide chain, resulting in a ''peptide-amphiphile.'' The alignment o f amphiphilic compounds at the lipid-solvent interface is used to faci litate peptide alignment and structure initiation and propagation, whi le the lipophilic region adsorbs to hydrophobic surfaces. Peptide-amph iphiles containing potentially triple-helical or alpha-helical structu ral motifs have been synthesized. The resultant head group structures have been characterized by CD spectroscopy and found to be thermally s table over physiological temperature ranges. Triple-helical peptide-am phiphiles have been applied to studies of surface modification and cel l receptor binding. Cell adhesion and spreading was promoted by triple -helical peptide-amphiphiles. Cellular interaction with the type IV co llagen sequence alpha 1(IV) 1263-1277 increased signal transduction, w ith both the time mid level of induction dependent upon triple-helical conformation. Collectively, these results suggest that peptide-amphip hiles may be used to form stable molecular structures on biomaterial s urfaces that promote cellular activities and improve biocompatibility. (C) 1998 John Wiley & Sons, Inc.