Nonlinear Relationships of Fibrin Network Structure as a Function of Fibrinogen and Thrombin Concentrations for Purified Fibrinogen and Plasma Clots

Background Fibrinogen levels are associated with bleeding disorders and thrombotic disease. Thrombin converts fibrinogen to fibrin, producing the load-bearing fibrin scaffold that governs clot mechanics and transport. Objective Quantitatively map how fibrinogen and thrombin concentrations program fibrin architecture in human plasma and purified Peak 1 fibrinogen. Methods Scanning electron microscopy quantified single-fiber morphology—fiber diameter and branch-to-branch segment length from a standardized sample-preparation protocol. Confocal microscopy quantified network architecture (projected fiber density and pore/bubble size). Results and Conclusions Across plasma and purified systems, diverse readouts collapsed onto compact multiplicative scaling laws . The exponent patterns reveal a division of labor: thrombin primarily controls single-fiber growth kinetics, strongly shortening branch-to-branch segment length and modestly thinning fibers, whereas fibrinogen primarily controls space filling, strongly increasing fiber density and reducing pore/bubble size while thickening fibers. Network metrics further followed an approximately geometric packing relation (pore/bubble size ∝ fiber density -1/2 ) across systems. For matched [ Fgn ] 0 and [ Thr ] 0 , purified fibrinogen formed denser networks with smaller pores than plasma, consistent with environment-dependent effective assembly conditions. These parameterized scaling relations allow prediction linking composition to fibrin microstructure across plasma and purified fibrinogen clots, and they motivate a mechanistic picture in which thrombin sets the kinetic/length scale of single-fiber growth while fibrinogen tunes space-filling architecture. Fiber length analysis suggests that each thrombin molecule nucleates one fiber. These relationships provide the baseline for extensive, quantitative modeling work of blood clotting.