IN-VITRO ANGIOGENESIS IS MODULATED BY THE MECHANICAL PROPERTIES OF FIBRIN GELS AND IS RELATED TO ALPHA(V)BETA(3) INTEGRIN LOCALIZATION

This study deals with the role of the mechanical properties of matrice s in in vitro angiogenesis. The ability of rigid fibrinogen matrices w ith fibrin gels to promote capillarylike structures was compared. The role of the mechanical properties of the fibrin gels was assessed by v arying concentration of the fibrin gels. When the concentration of fib rin gels was decreased from 2 mg/ml to 0.5 mg/ml, the capillarylike ne twork increased. On rigid fibrinogen matrices, capillarylike structure s were not formed. The extent of the capillarylike network formed on f ibrin gels having the lowest concentration depended on the number of c ells seeded. The dynamic analysis of capillarylike network formation p ermitted a direct visualization of a progressive stretching of the 0.5 mg/ml fibrin gels. This stretching was not observed when fibrin conce ntration increases. This analysis shows that 10 h after seeding, a pre arrangement of cells into ringlike structures was observed. These ring like structures grew in size. Between 16 and 24 h after seeding, the c apillarylike structures were formed at the junction to two ringlike st ructures. Analysis of the alpha(v)beta(3) integrin localization demons trates that cell adhesion to fibrinogen is mediated through the alpha( v)beta(3) integrin localized into adhesion plaques. Conversely, cell a dhesion to fibrin shows a diffuse and dot-contact distribution. We sug gest that the balance of the stresses between the tractions exerted by the cells and the resistance of the fibrin gels triggers an angiogeni c signal into the intracellular compartment. This signal could be asso ciated with modification in the alpha(v)beta(3) integrin distribution.