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Title: The Viscoelastic Properties of Fibrin Clots Studied Using Magnetic Tweezers
Author: Harrand, Robert
ISNI:       0000 0001 3532 5233
Awarding Body: The University of Leeds
Current Institution: University of Leeds
Date of Award: 2007
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Magnetic tweezers have been designed, constructed, calibrated and 'applied, for the first time, to the study of the mechanical properties of fibrin clots. Three-dimensional control over magnetic particle position was achieved with forces of ''100pN in X,Y and ''IOpN in Z, generated with 4.5JLm ·particles. Software was custom written to control both the operation of the electromagnets and data analysis of the-captured images. The performance of the magnetic tweezers was initially evaluated using model viscous and viscoelastic materials such as polyacrylamide, and was used to demonstrate that the viscosity of complex fluids such as protein solutions could be measured. The calibrated magnetic tweezers were then applied to the study of the viscoelastic properties of fibrin clot formation using recombinant and purified fibrinogen in collaboration with colleagues in the Leeds General Infirmary. The behaviour of wild type fibrinogen was compared with three variants, each of which had particular physiological releyance. Initial results revealed a Hookean response of the fibrin clots at low forces, strain hardening at higher forces, and an increase to a maximum value of G' over time. Des-B,BI-42, which is created by the enzymatic action of rattlesnake venom, showed a marked reduction in mechanical strength compared with wild type fibrin, and this was related to thinner fibrin fibres by atomic force microscopy studies and turbidity measurements. The polymorphism. B,BArg448Lys, a relatively common variant with a frequency of 10-15% in Caucasians, possesses an argenine to lysine substitution in the ,B-chain region, 13 amino acids away from the carboxyl-terminal. A marked increase in clot stiffness was observed for the 448Lys variant compared to the 448Arg type, in agreement with known links between ,B-chain polymorphisms and coronary heart disease. Addition of the crosslinker factor XIII increased clot stiffness in both fibrin types, with increases in Lys448 clot stiffness continuing after several hours. Fibrinogen samples from patients with type 1 diabetes taken before and after treatment were studied to investigate possible links between the patient's blood sugar control and clotting functions. A k~y symptom of dia betes is an increased level of clot stiffness, increasing the risk of myocardial infarction. Results reveal~ a positive correlation between improvements in sugar control and reductions in clot stiffness.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available