Effect of homo poly(L-amino acids) on fibrin assembly: role of charge and molecular weight.
Positively charged molecules such as protamine, leukocyte cationic protein, and the carboxyl terminus of platelet factor 4 have been shown to increase fibrin fiber thickness. Synthetic homo poly(L-amino acids) were used to explore the role of charge and molecular weight of cationic molecules on fibrin assembly. The effects of poly(L-lysine) (PLL), poly(L-glutamic acid) (PLG), poly(L-aspartic acid) (PLA), poly(L-histidine) (PLH), and poly(L-arginine) (PLArg) on the assembly and structure of fibrin gels were studied by using light-scattering techniques. At a PLG (Mr 60,000) concentration of 80 micrograms/mL and a PLA (Mr 20,000) concentration of 64 microgram/mL, neither of these negatively charged polymers produced a detectable change in either fibrin assembly kinetics or final structure. Positively charged PLArg (16 micrograms/mL) caused a 30% increase in fibrin fiber mass/length ratio without calcium. In contrast, PLH (16 micrograms/mL), also positively charged, had no effect in the absence of CaCl2 but produced a 40% increase in fiber mass/length ratio with 5 mM CaCl2. At concentrations as low as 1 microgram/mL, positively charged PLL increased the initial fibrin assembly kinetics and led to larger fiber mass/length ratio. The impact on fibrin mass/length ratio was equivalent for three different molecular weight preparations of PLL (Mr 25,000, 90,000, and 240,000). The lack of a molecular weight effect on fiber thickness and the low polymer concentrations required to produce the perturbation argue against an excluded volume effect as the mechanism by which lateral fiber growth is augmented. Mechanisms by which poly(L-amino acids) may perturb fibrin assembly are discussed.
Carr
M E
ME
Department of Medicine, Medical College of Virginia, Richmond 23249.
Cromartie
R
R
Gabriel
D A
DA
D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005782:Gels; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D010455:Peptides / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D005782:Gels; D046911:Macromolecular Substances; D010455:Peptides; D005337:Fibrin; D005340:Fibrinogen