Abstract
We have examined the effects of an integrin-binding competitor, echistatin, in solution on adhesion and migration of rat microvessel endothelial cells on fibronectinin vitro. A biphasic dependence of cell motility on fibronectin surface density was observed, with a peak random motility coefficient of about 8 × 10−9 cm2/sec occurring below 0.3 μg/cm2 fibronectin. In the presence of echistatin at 0.5 μM, the peak random motility coefficient was similar but occurred at the significantly greater fibronectin surface density of 1.2 μg/cm2. Hence, the same concentration of this soluble integrin-binding competitor inhibited migration on low fibronectin densities but enhanced migration on high fibronectin densities. At the same time, echistatin decreased adhesiveness on all fibronectin surface densities. When motility was correlated explicitly with adhesiveness, a single biphasic relationship was obtained for both absence and presence of echistatin with peak motility occuring in both cases at identical adhesiveness. Both the inhibiting and enhancing effects of the soluble integrin-binding competitor on motility are predictable from its effect on adhesion, consistent with the theoretical models of Lauffenburger (15) and DiMillaet al. (3).
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Boucaut, J.C.; Darribere, T.; Poole, T.J.; Aoyama, H.; Yamada, K.M.; Thiery, J.P. Biologically active synthetic peptides as probes of embryonic development: A competitive peptide inhibitor of fibronectin function inhibits gastrulation in amphibian embryos and neural crest cell migration. J. Cell Biol. 99:1822–1830; 1984.
Chu, L.; Tempelman, L.A.; Miller, C.; Hammer, D.A. Centrifugation assay for receptor-mediated cell adhesion of IgE-sensitized rat basophilic leukemia cells to antigencoated polyacrylamide gels. AIChE J. (accepted for publication).
DiMilla, P.A.; Barbee, K.; Lauffenburger, D.A. Mathematical model for the effects of adhesion and mechanics on cell migration speed. Biophys. J. 60:15–37; 1991.
DiMilla, P.A.; Albelda, S.M.; Quinn, J.A. Adsorption and elution of extracellular matrix proteins on non-tissue culture polystyrene petri dishes. J. Coll. Int. Sci. 153:212–225; 1992.
DiMilla, P.A.; Stone, J.A.; Quinn, J.A.; Albelda, S.M.; Lauffenburger, D.A. An optimal adhesiveness exists for human smooth muscle cell migration on type IV collagen and fibronectin. J. Cell Biol. 122:729–737; 1993.
D'Souza, S.E.; Ginsberg, M.H.; Plow, E.F. Arginylglycyl-aspartic acid (RGD): a cell adhesion motif. Trends Biochem. Sci. 16:246–250; 1991.
Edelman, G.M.; Crossin, K.L. Cell adhesion molecules: Implications for a molecular histology. Annu. Rev. Biochem. 60:155–190; 1991.
Farrell, B.E.; Daniele, R.P.; Lauffenburger, D.A. Quantitative relationships between single-cell and cell-population model parameters for chemosensory migration responses of alveolar macrophages to C5a. Cell Motility Cytoskel. 16: 279–293; 1990.
Gamble, J.R.; Matthias, L.J.; Meyer, G.; Kaur, P.; Russ, G.; Faull, R.; Berndt, M.C.; Vadas, M.A. Regulation ofin vitro capillary tube formation by anti-integrin antibodies. J. Cell Biol. 121:931–943; 1993.
Goodman, S.L.; Risse, G.; von der Mark, K. The E8 subfragment of laminin promotes locomotion of myoblasts over extracellular matrix. J. Cell Biol. 109:799–809; 1989.
Gould, R.J.; Polokoff, M.A.; Friedman, P.A.; Huang, T.-F.; Holt, J.C.; Cook, J.J.; Niewiarowski, S. Disintegrin. A family of integrin inhibitory proteins from viper venoms. Proc. Soc. Exp. Biol. Med. 195:168–171; 1990.
Humphries, M.J.; Olden, K.; Yamada, K.M. A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science 233:457–470; 1986.
Ingber, D.E.; Folkman, J. How does extracellular matrix control capillary morphogenesis? Cell 59:803–805; 1989.
Larson, H.J. Introduction to Probability Theory and Statistical Inference, 3rd edition, New York: John Wiley & Sons, 1982, 637 pp.
Lauffenburger, D.A. A simple model for effects of receptormediated cell-substratum adhesion on cell migration. Chem. Eng. Sci. 44:1903–1914; 1989.
Lauffenburger, D.A.; Linderman, J.J. Receptors: Models for Binding, Trafficking, and Signaling. Oxford University Press, 1993, 365 pp.
McClay, D.R.; Wessel, G.M.; Marchase, R.B. Intercellular recognition: Quantitation of initial binding events. Proc. Natl. Acad. Sci. 78:4975–4979; 1981.
Nicosia, R.F.; Bonanno, E. Inhibition of angiogenesisin vitro by arg-gly-asp-containing synthetic peptide. Am. J. Pathol. 138:829–833; 1991.
Nicosia, R.F.; Bonanno, E.; Smith, M. Fibronectin promotes the elongation of microvessels during angiogenesisin vitro. J. Cell. Physiol. 154:654–661; 1993.
Ruoslahti, E. Integrins. J. Clin. Invest. 87:1–5; 1991.
Ruoslahti, E.; Giancotti, F.G. Integrins and tumor cell dissemination. Canc. Cells 1:119–126; 1989.
Ruoslahti, E.; Piersbacher, M.D. New perspectives in cell adhesion: RGD and integrins. Science 238:491–497; 1987.
Rupnick, M.A.; Stokes, C.L.; Williams, S.K.; Lauffenburger, D.A. Quantitative analysis of random motility of human microvessel endothelial cells using a linear underagarose assay. Lab. Invest. 59:363–372; 1988.
Savage, B.; Marzee, U.M.; Chao, B.H.; Harker, L.A.; Maraganore, J.M.; Ruggeri, Z.M. Binding of the snake venomderived proteins applaggin and echistatin to the arginineglycine-aspartic acid recognition site(s) on platelet glycoprotein IIb. IIIa complex inhibits receptor function. J. Biol. Chem. 265:11766–11772; 1990.
Stokes, C.L.; Williams, S.K.; Lauffenburger, D.A. Migration of individual microvessel endothelial cells: Stochastic model and parameter measurement. J. Cell Sci. 99:419–430; 1991.
Wagner, R.; Mathews, M. The isolation and culture of capillary endothelium from epididymal fat. Microvasc. Res. 10:286–297; 1975.
Williams, S.K. Isolation and culture of microvessel endothelial cells: their use in transplant and clinical studies. In: Microvascular Perfusion and Transplant in Health and Disease, edited by P. McDonagh. Basel, Switzerland: Karger, 1987, pp. 204–224.
Williams, S.K.; Jarrell, B.E.; Rose, D.G. Isolation of human fat-derived microvessel endothelial cells for use in vascular graft endothelialization. In: Endothelialization of Vascular Grafts, edited by P. Zilla, Basel, Switzerland: Karger, 1987, pp. 211–217.
Zigmond, S.H.; Lauffenburger, D.A. Assays for leukocyte chemotaxis. Annu. Rev. Med. 37:149–155; 1986.
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Wu, P., Hoying, J.B., Williams, S.K. et al. Integrin-binding peptide in solution inhibits or enhances endothelial cell migration, predictably from cell adhesion. Ann Biomed Eng 22, 144–152 (1994). https://doi.org/10.1007/BF02390372
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DOI: https://doi.org/10.1007/BF02390372