Design of a novel fibronectin-mimetic peptide-amphiphile for functionalized biomaterials.
The interaction of the alpha5beta1 integrin with its ligand, fibronectin, supports numerous adhesive functions and has an important role in health and disease. In recent years, there has been a considerable effort in designing fibronectin-mimetic peptides to target the integrin. However, to date, the therapeutic use of these peptides has been limited, as they cannot accurately mimic fibronectin's binding affinity for alpha5beta1. A peptide-amphiphile (PR_b) was synthesized with a peptide headgroup composed of four building blocks: a spacer; RGDSP, the primary recognition site for alpha5beta1; PHSRN, the synergy binding site; and a linker. The linker was designed to mimic two important criteria: the distance and the hydrophobicity/hydrophilicity between PHSRN and RGD in fibronectin. Human umbilical vein endothelial cells were seeded on different substrates and evaluated in terms of adhesion, spreading, specificity, cytoskeleton organization, focal adhesions, and secretion of extracellular fibronectin. This peptide was shown to perform comparably to fibronectin, indicating that a biomimetic approach can result in the design of novel peptides with therapeutic potential for biomaterial functionalization.
Mardilovich
Anastasia
A
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Craig
Jennifer A
JA
McCammon
Matthew Q
MQ
Garg
Ashish
A
Kokkoli
Efrosini
E
D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry; D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D005353:Fibronectins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D039081:Integrin alpha5beta1 / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D014471:Umbilical Veins / Q000166:cytology* / Q000502:physiology
D005353:Fibronectins; D039081:Integrin alpha5beta1; D009842:Oligopeptides; D010446:Peptide Fragments; C495978:prolyl-histidyl-seryl-arginyl-asparagine; C047981:arginyl-glycyl-aspartic acid