In vitro angiogenesis is modulated by the mechanical properties of fibrin gels and is related to αvβ3 integrin localization
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This study deals with the role of the mechanical properties of matrices in in vitro angiogenesis. The ability of rigid fibrinogen matrices with fibrin gels to promote capillarylike structures was compared. The role of the mechanical properties of the fibrin gels was assessed by varying concentration of the fibrin gels. When the concentration of fibrin gels was decreased from 2 mg/ml to 0.5 mg/ml, the capillarylike network increased. On rigid fibrinogen matrices, capillarylike structures were not formed. The extent of the capillarylike network formed on fibrin gels having the lowest concentration depended on the number of cells seeded. The dynamic analysis of capillarylike network formation permitted a direct visualization of a progressive stretching of the 0.5 mg/ml fibrin gels. This stretching was not observed when fibrin concentration increases. This analysis shows that 10 h after seeding, a prearrangement of cells into ringlike structures was observed. These ringlike structures grew in size. Between 16 and 24 h after seeding, the capillarylike structures were formed at the junction of two ringlike structures. Analysis of the αvβ3 integrin localization demonstrates that cell adhesion to fibrinogen is mediated through the αvβ3 integrin localized into adhesion plaques. Conversely, cell adhesion to fibrin shows a diffuse and dot-contact distribution. We suggest that the balance of the stresses between the tractions exerted by the cells and the resistance of the fibrin gels triggers an angiogenic signal into the intracellular compartment. This signal could be associated with modification in the αvβ3 integrin distribution.
Key wordsendothelial cell neovascularization in vitro fibrin matrix mechanical properties dynamic analysis αvβ3 integrins
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- 1.Allen, R. D.; Allen, N. S.; Travis, J. L. Video-enhanced contrast, differential interference contrast (AVEC-DIC) microscopy: a new method capable of analysing microtubule-related motility in the reticulopodial network of Allogromia paticollaris. Cell Motil. 1:291–302; 1981.PubMedCrossRefGoogle Scholar
- 5.Bretscher, M. S. Cells use their transferrin receptors for locomotion. Eur. Mol. Biol. Organ. J. 11:393–389; 1992.Google Scholar
- 9.Cotran, R. S.; Kumar, V.; Robbins, S. L. Inflammation and repair. In: Pathologic basis of disease, 4th ed. London: W. B. Saunders. 1990: 39–86.Google Scholar
- 15.Folkman, J. Diagnostic and therapeutic application of angiogenesis research. C.R. Acad. Sci. III 16:914–918; 1993.Google Scholar
- 22.Guenet, J. M. Thermoreversible gelation of polymers and biopolymers. London: Academic Press; 1992.Google Scholar
- 23.Guidry, C.; Grinnell, G. Contraction of hydrated collagen gels by fibroblasts: evidence for two mechanisms by which collagen fibrils are stabilized. Collagen Relat. Res. 6:515–529; 1986.Google Scholar
- 24.Hynes, R. O. Wound healing, inflammation, and fibrosis. In: Fibronectins. New York: Springer-Verlag; 1990:349–364.Google Scholar
- 33.Keckwick, R. A.; McKay, M. E.; Nance, M. H., et al. The purification of human fibrinogen. Biochem. J. 60:671–683; 1955.Google Scholar
- 40.Pepper, M. S.; Vassalli, J. D.; Orci, L., et al. Angiogenesis in vitro: cytokines interactions and balanced extracellular proteolysis. In: Maragoudakis, M. E., et al., eds. Angiogenesis: molecular biology, clinical aspects. New York: Plenum Press; 1994.Google Scholar