Protein-like molecular architecture: biomaterial applications for inducing cellular receptor binding and signal transduction.
The development of biomaterials with desirable biocompatibility has presented a difficult challenge for tissue engineering researchers. First and foremost, materials themselves tend to be hydrophobic and/or thrombogenic in nature, and face compatibility problems upon implantation. To mediate this problem, researchers have attempted to graft protein fragments onto biomaterial surfaces to promote endothelial cell attachment and minimize thrombosis. We envisioned a novel approach, based on the capability of biomolecules to self-assemble into well-defined and intricate structures, for creating biomimetic biomaterials that promote cell adhesion and proliferation. One of the most intriguing self-assembly processes is the folding of peptide chains into native protein structures. We have developed a method for building protein-like structural motifs that incorporate sequences of biological interest. A lipophilic moiety is attached onto a N alpha-amino group of peptide chain, resulting in a "peptide-amphiphile." The alignment of amphiphilic compounds at the lipid-solvent interface is used to facilitate peptide alignment and structure initiation and propagation, while the lipophilic region absorbs to hydrophobic surfaces. Peptide-amphiphiles containing potentially triple-helical or alpha-helical structural motifs have been synthesized. The resultant head group structures have been characterized by CD spectroscopy and found to be thermally stable over physiological temperature ranges. Triple-helical peptide-amphiphiles have been applied to studies of surface modification and cell receptor binding. Cell adhesion and spreading was promoted by triple-helical peptide-amphiphiles. Cellular interaction with the type IV collagen sequence alpha 1(IV) 1263-1277 increased signal transduction, with both the time and level of induction dependent upon triple-helical conformation. Collectively, these results suggest that peptide-amphiphiles may be used to form stable molecular structure on biomaterial surfaces that promote cellular activities and improve biocompatibility.
Fields
G B
GB
Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton 33431, USA.
Lauer
J L
JL
Dori
Y
Y
Forns
P
P
Yu
Y C
YC
Tirrell
M
M
D000595:Amino Acid Sequence; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002942:Circular Dichroism; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D011233:Precipitin Tests; D017433:Protein Structure, Secondary; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D001672:Biocompatible Materials; D010455:Peptides; D003094:Collagen