Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-14T18:41:08.652Z Has data issue: false hasContentIssue false

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
Get access

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Lanza, R. P, Langer, R. S.; Vacanti, J., Principles of tissue engineering. 2nd ed.; Academic Press: San Diego, CA, 2000; ‘Vol.’ p xli, 995.Google Scholar
2. Harrison, D.; Johnson, R.; Tucci, M.; Puckett, A.; Tsao, A.; Hughes, J.; Benghuzzi, H., Interaction of cells with UHMWPE impregnated with the bioactive peptides RGD, RGE or Poly-L-lysine. Biomed Sci Instrum 1997, 34, 41–6.Google Scholar
3. Rezania, A.; Healy, K. E., The effect of peptide surface density on mineralization of a matrix deposited by osteogenic cells. J Biomed Mater Res 2000, 52, (4), 595600.Google Scholar
4. Maheshwari, G.; Brown, G.; Lauffenburger, D. A.; Wells, A.; Griffith, L. G., Cell adhesion and motility depend on nanoscale RGD clustering. J Cell Sci 2000, 113 (Pt 10), 1677–86.Google Scholar
5. Lee, K. Y.; Mooney, D. J., Hydrogels for tissue engineering. Chem Rev 2001, 101, (7), 1869–79.Google Scholar
6. Rowley, J. A.; Madlambayan, G.; Mooney, D. J., Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 1999, 20, (1), 4553.Google Scholar
7. Lee, K.Y., Alsberg, E., Hsiong, S., Comisar, W., Linderman, J., Ziff, R., and Mooney, D.J., Nanoscale Adhesion Ligand Organization Regulates Osteoblast Proliferation and Differentiation. Nanoletters 2004, 4, (8), 15011506.Google Scholar
8. Alsberg, E.; Anderson, K. W.; Albeiruti, A.; Franceschi, R. T.; Mooney, D. J., Cell-interactive alginate hydrogels for bone tissue engineering. J Dent Res 2001, 80, (11), 2025–9.Google Scholar
9. Diduch, D. R.; Coe, M. R.; Joyner, C.; Owen, M. E.; Balian, G., Two cell lines from bone marrow that differ in terms of collagen synthesis, osteogenic characteristics, and matrix mineralization. J Bone Joint Surg Am 1993, 75, (1), 92105.Google Scholar