title: Quantifying the relation between bond number and myoblast proliferation.
abstract: Many functions of the extracellular matrix can be mimicked by small peptide fragments (e.g., arginine-glycine-aspartic acid (RGD) sequence) of the entire molecule, but the presentation of the peptides is critical to their effects on cells. It is likely that some effects of peptide presentation from biomaterials simply relate to the number of bonds formed between cell receptors and the adhesion ligands, but a lack of tools to quantify bond number limits direct investigation of this assumption. The impact of different ligand presentations (density, affinity, and nanoscale distribution) on the proliferation of C2C12 and human primary myoblasts was first examined in this study. Increasing the ligand density or binding affinity led to a similar enhancement in proliferation of C2C12 cells and human primary myoblasts. The nanoscale distribution of clustered RGD ligands also influenced C2C12 cells and human primary myoblast proliferation, but in an opposing manner. A theological technique and a FRET technique were then utilized to quantify the number of receptor-ligand interactions as a function of peptide presentation. Higher numbers of bonds were formed when the RGD density and affinity were increased, as measured with both techniques, and bond number correlated with cell growth rates. However, the influence of the nanoscale peptide distribution did not appear to be solely a function of bond number. Altogether, these findings provide significant insight to the role of peptide presentation in the regulation of cell proliferation, and the approaches developed in this work may have significant utility in probing how adhesion regulates a variety of other cellular functions and aid in developing design criterion for cell-interactive materials.
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Tanyarut
authors.initials: T
authors.lastname: Boontheekul
authors.forename: Hyun-Joon
authors.initials: HJ
authors.lastname: Kong
authors.forename: Susan X
authors.initials: SX
authors.lastname: Hsiong
authors.forename: Yen-Chen
authors.initials: YC
authors.lastname: Huang
authors.forename: L
authors.initials: L
authors.lastname: Mahadevan
authors.forename: Herman
authors.initials: H
authors.lastname: Vandenburgh
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D051379:Mice; D032446:Myoblasts / Q000502:physiology*; D009842:Oligopeptides / Q000378:metabolism*; D010641:Phenotype; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism; D018000:Receptors, Peptide / Q000032:analysis / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor; C047981:arginyl-glycyl-aspartic acid