Collagen-induced platelet aggregation and release. II Critical size and structural requirements of collagen.

Abstract It has been suggested that polymerization of collagen molecules possessing an intact tertiary structure is a prerequisite for collagen to induce platelet aggregation and release. In the present study the critical size and structural requirements of collagen polymers for collagen-platelet interaction were determined. The effects of fibrous-long-spacing and short periodicity collagen polymers on platelet aggregation and release of serotonin were found to be the same as that of native-type collagen fibers, whereas segment-long-spacing as well as amorphous collagen did not induce platelet aggregation and release of serotonin. These results suggest that a regular arrangement of the collagen monomers in a staggered, repetitive structure may be essential for interaction with blood platelets. To correlate the length of collagen polymer with the parameters associated with platelet aggregation and release, soluble collagen polymers were prepared from monomeric collagen by dialysis against distilled water at 1, 3 and 4 h intervals or against 0.001 M acetate buffers (pH 3.6, 4.2, 4.4 and 5.0). The latter gave a less polydisperse solution than the former as determined by viscometry and flow birefringence. The length distributions were from 4500 A to 18 000 A. Results indicate that monomeric collagen solution (molecular length 3000 A) at a final concentration of 8 μg/ml failed to induce either platelet aggregation or serotonin release whereas polymeric collagen solution at the same concentration behaved differently. At pH 4.4 the molecular length distribution of collagen was 7−4.5·10 3 A and it induced a platelet shape change and a slight degree of aggregation. When the length distribution was 10−7· 10 3 A at pH 5.0, the collagen became active and caused an immediate platelet shape change and complete aggregation. These data suggest that a collagen polymer possessing a particle size of about three molecular lengths (9000 A) is the minimum length required. Furthermore, lateral aggregation of collagen monomers are inactive in inducing platelet aggregation and release.