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

Area of Science:

• Biochemistry
• Hematology
• Materials Science

Background:

• Thrombus stability relies on fibrin networks and neutrophil extracellular traps (NETs).
• NETs comprise DNA and histones, with linear polyphosphates (PolyP) known to enhance their fibrin-stabilizing properties.
• The role of in vivo polyphosphate nanoparticles (PolyP-NP) in the fibrin/NET matrix is not well understood.

Purpose of the Study:

• To compare the effects of linear PolyP and PolyP-NP on fibrin formation, structure, and lysis.
• To investigate the interactions of PolyP with NET components, specifically histone H3.
• To assess the influence of PolyP form (linear vs. nanoparticle) on thrombus stability.

Main Methods:

• Transmission electron microscopy and dynamic light scattering for PolyP-NP characterization.
• Turbidimetry to measure fibrin formation and lysis kinetics.
• Scanning electron microscopy for fibrin structure analysis and surface plasmon resonance for histone-PolyP interactions.

Main Results:

• Both linear PolyP and PolyP-NP accelerated fibrin formation and slowed lysis, effects dependent on particle number, not size.
• PolyP-NP, unlike linear PolyP, enhanced histone-mediated prolongation of lysis time and fibrin fiber thickening.
• PolyP-NP exhibited weaker binding to histone compared to linear PolyP.

Conclusions:

• Polyphosphate interaction with histone significantly modulates fibrin formation and lysis.
• Polyphosphate nanoparticles enhance thrombus stabilization by histone more effectively than linear polyphosphates.
• The form of polyphosphate (nanoparticle vs. linear) influences its impact on thrombus mechanical and lytic properties.