title: Thrombin flux and wall shear rate regulate fibrin fiber deposition state during polymerization under flow.
abstract: Thrombin is released as a soluble enzyme from the surface of platelets and tissue-factor-bearing cells to trigger fibrin polymerization during thrombosis under flow conditions. Although isotropic fibrin polymerization under static conditions involves protofibril extension and lateral aggregation leading to a gel, factors regulating fiber growth are poorly quantified under hemodynamic flow due to the difficulty of setting thrombin fluxes. A membrane microfluidic device allowed combined control of both thrombin wall flux (10(-13) to 10(-11) nmol/mum(2) s) and the wall shear rate (10-100 s(-1)) of a flowing fibrinogen solution. At a thrombin flux of 10(-12) nmol/mum(2) s, both fibrin deposition and fiber thickness decreased as the wall shear rate increased from 10 to 100 s(-1). Direct measurement and transport-reaction simulations at 12 different thrombin flux-wall shear rate conditions demonstrated that two dimensionless numbers, the Peclet number (Pe) and the Damkohler number (Da), defined a state diagram to predict fibrin morphology. For Da < 10, we only observed thin films at all Pe. For 10 < Da < 900, we observed either mat fibers or gels, depending on the Pe. For Da > 900 and Pe < 100, we observed three-dimensional gels. These results indicate that increases in wall shear rate quench first lateral aggregation and then protofibril extension.
authors.affiliation: Department of Chemical Engineering, Colorado School of Mines, Golden, Colorado, USA. kneeves@mines.edu
authors.forename: K B
authors.initials: KB
authors.lastname: Neeves
authors.forename: D A R
authors.initials: DA
authors.lastname: Illing
authors.forename: S L
authors.initials: SL
authors.lastname: Diamond
mesh_terms: D001703:Biophysics / Q000379:methods*; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003198:Computer Simulation; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D005782:Gels; D006801:Humans; D044085:Microfluidics; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011108:Polymers / Q000737:chemistry*; D013314:Stress, Mechanical; D013917:Thrombin / Q000737:chemistry*; D013927:Thrombosis / Q000473:pathology
chemical_list: D005782:Gels; D011108:Polymers; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin