Divalent cations induce protofibril gelation

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Abstract
Soluble fibrin oligomers (protofibrils) undergo phase change merely by adding 1–2 mM Ca2+ 25‐100 μM Zn2+. The cation‐induced “protofibrin” clots appear similar to normally formed fibrin gels. Maximal clot turbidity of protofibrin gels increases with cations in a concentration‐dependent manner. Magnesium (less than 0.5 mM) is ineffective in inducing protofibril gelation. Turbidity and degree of polymerization (DP) [indirectly expressed as AT (activation time)] appear to be positively correlated, regardless of whether the divalent cation is Ca2+ or Zn2+. Cross sections of Ca2+‐induced protofibrin fibers are ∼6–18‐fibrin‐monomers‐thick. With both Ca2+ and 40 μM Zn2+, fiber cross section increases to 30–50 monomers thick. Negatively stained Zn2+,‐ and Ca2+‐induced protofibrin gels exhibit banding periodicity of ∼ 240 Å, similar to that of normally generated fibrin gels. Regions of lateral merging of individual segments of the protofibrin leads to increased cross section of the fiber and forms a branch required for gelation. These findings indicate that the rate of coagulation and the ultimate thickness of the fibers both relate to lateral associative processes of protofibrils, which are augmented by physiologic concentrations of2+ and Zn2+.