Study on the oxidation of fibrinogen using Fe3O4 magnetic nanoparticles and its influence to the formation of fibrin

Abstract

Oxidative stress accompanies various diseases associated with chronic inflammation. In this work, H2O2 and H2O2–Fe3O4 magnetic nanoparticles were used as two reactive oxygen species to study the oxidative stress for the structure and polymerization behaviour of fibrinogen molecules. The alterations of secondary structure and component of fibrinogen molecule were characterized by circular dichroism spectra, ultraviolet-visible spectra and fluorescence spectra, the viscoelasticity of fibrinogen solution was studied by dynamic light scattering microrheology. Based on the molecular dynamics simulations and fluorescence properties, the possible oxidative stress sites were analyzed and confirmed by Tb3+ probe. The hydrophobicity/philicity and electrostatic net charges present on the exterior part of the fibrinogen molecules were measured with zeta potential. The height and image analysis obtained from atomic force microscope indicated that oxidative stress of fibrinogen molecules could influence the equilateral junctions of protofibrils and the different cross-linking patterns between the α- and γ-chains, result in the decrease of the fibre size, form a higher proportion of branching and a denser aggregation state. This study will provide insights into the misfolding and fibril formation of disease-associated fibrinogen, facilitate an increased understanding of how oxidative stress in vivo affects the formation and polymerization of fibrin, and support efforts for the improved treatment of patients suffering from the thrombotic disease.