Polyphosphate nanoparticles enhance the fibrin stabilization by histones more efficiently than linear polyphosphates

• Published in: PloS one 2022-04, Vol.17 (4), p.e0266782-e0266782
• Main Authors: Lovas, Miklós, Tanka-Salamon, Anna, Beinrohr, László, Voszka, István, Szabó, László, Molnár, Kinga, Kolev, Krasimir
• Format: Article
• Language: English
• Subjects: Analysis; Biochemistry; Biology; Biology and life sciences; Biophysics; Clotting; Deoxyribonucleic acid; Dissolution; DNA; Dynamic stability; Electron microscopy; Engineering and Technology; Fibers; Fibrin; Fibrin - metabolism; Fibrinogen; Fibrinogen - metabolism; Histone H3; Histones; Humans; Leukocytes (neutrophilic); Light scattering; Lysis; Mathematical analysis; Maximum entropy method; Nanoparticles; Particle size; Phosphatase; Photon correlation spectroscopy; Physical Sciences; Polyanions; Polyelectrolytes; Polyphosphates; Polyphosphates - metabolism; Polyps; Prolongation; Properties; Radiation; Scanning electron microscopy; Surface plasmon resonance; Thickening; Thrombin; Thrombin - metabolism; Thrombosis; Thrombosis - metabolism; Transmission electron microscopy; Turbidimetry
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0266782

Beyond the three-dimensional fibrin network, the mechanical and lytic stability of thrombi is supported by the matrix of neutrophil extracellular traps (NETs) composed of polyanionic DNA meshwork with attached proteins including polycationic histones. Polyphosphates represent another type of polyanions, which in their linear form are known to enhance the fibrin stabilizing effects of DNA and histones. However, in vivo polyphosphates are also present in the form of nanoparticles (PolyP-NP), the interference of which with the fibrin/NET matrix is poorly characterized. To compare the effects of linear and nanoparticulate polyphosphates, and their combinations with relevant NET components (DNA, histone H3) on fibrin formation, structure, and lysis in in vitro assays focusing on histone-polyphosphate interactions. Transmission electron microscopy and dynamic light scattering for stability of the PolyP-NP preparations. Turbidimetry for kinetics of fibrinogen clotting by thrombin and fibrin dissolution by tissue-type plasminogen activator/plasminogen. Scanning electron microscopy for fibrin structure. Surface plasmon resonance for strength of histone-PolyP interactions. Both linear PolyP and PolyP-NP accelerated the fibrin formation and slowed down its dissolution and these effects were strongly dependent on the number of individual PolyP particles and not on their size. Addition of DNA did not modify significantly the PolyP-NP effects on fibrin formation and lysis. Both linear and nanoparticulate PolyP counteracted the effect of histone in the acceleration of fibrinogen clotting by thrombin. PolyP-NP, but not linear PolyP enhanced the prolongation of lysis time in fibrin containing histone and caused more pronounced thickening of the fibrin fibers than the linear form. Finally, PolyP-NP bound weaker to histone than the linear form. The interaction of PolyP with histone was a stronger modulator of fibrin formation and lysis than its interaction with DNA. In addition, the PolyP nanoparticles enhanced the thrombus stabilizing effects of histone more effectively than linear PolyP.