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Nanoscale RGD Peptide Organization Regulates Cell Proliferation and Differentiation

Published online by Cambridge University Press:  01 February 2011

Susan Hsiong
Affiliation:
Department of Chemical Engineering, Harvard University Laboratory for Cell and Tissue Engineering 40 Oxford St., Rm. 415 ESL Cambridge, MA 02138 University of Michigan, Ann Arbor, MI.Division of Engineering and Applied Sciences, Harvard University Laboratory for Cell and Tissue Engineering 40 Oxford St., Rm. 415 ESL Cambridge, MA 02138
Kuen Yong Lee
Affiliation:
Biologic & Materials Science, Harvard University Laboratory for Cell and Tissue Engineering 40 Oxford St., Rm. 415 ESL Cambridge, MA 02138
Eben Alsberg
Affiliation:
Biomedical Engineering, Harvard University Laboratory for Cell and Tissue Engineering 40 Oxford St., Rm. 415 ESL Cambridge, MA 02138
David Mooney
Affiliation:
Department of Chemical Engineering, Harvard University Laboratory for Cell and Tissue Engineering 40 Oxford St., Rm. 415 ESL Cambridge, MA 02138 University of Michigan, Ann Arbor, MI.Division of Engineering and Applied Sciences, Harvard University Laboratory for Cell and Tissue Engineering 40 Oxford St., Rm. 415 ESL Cambridge, MA 02138
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Abstract

RGD (arginine-glycine-aspartic acid) containing peptide sequences, common cell attachment sites present in many extracellular matrix (ECM) proteins, mediate many important cellular processes. The role of nanoscale organization of RGD peptides in the regulation of the adhesion, proliferation and differentiation of both preosteoblasts (MC3T3-E1) and multipotential (D1) cell lines in vitro was investigated in this study. Alginate polymer chains with varying RGD peptide degree of substitution were mixed with unmodified polymer chains at different ratios to allow variation of RGD peptide spacing in the nanometer scale, independently of the overall bulk density of peptides presented from the material. Proliferation of both cell types was observed to be closely correlated to RGD island (defined as a cluster of RGD peptides) spacing, independently of overall bulk ligand density, following cell adhesion to alginate hydrogels. Increased RGD island spacing was observed to promote spreading of MC3T3-E1 cells while simultaneously suppressing their proliferation. However, increased RGD island spacing decreased spreading of D1 cells while also decreasing proliferation. Moreover, differentiation of preosteoblasts was significantly upregulated in response to decreased RGD island spacing, whereas differentiation of multipotential cells was modestly regulated by this variable. These results demonstrate that the nanoscale organization of adhesion ligands may be an important variable in controlling cell phenotype and function. In addition, cellular responses to nanoscale ligand organization differ depending on the cell type, and this may be related to the differentiation stage of the cells.

Type
Research Article
Copyright
Copyright © Materials Research Society 2005

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References

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