Lipopolysaccharide supramolecular organization regulates the activation of coagulation factor XII

Abstract

Lipopolysaccharides (LPS) are key bacterial membrane components that activate coagulation factor XII (FXII), establishing a critical link between bacterial infections, blood coagulation, and inflammation. This study investigates how the supramolecular organization of LPS—monomers, micelles, and bilayers—affects FXII activation. We demonstrate that LPS micelles uniquely activate FXII to its enzymatic form (FXIIa), while monomeric LPS modulates FXIIa activity without direct activation, and bilayer-form LPS does not induce FXII activation. The addition of calcium ions (Ca²⁺) promoted the formation of bilayers by binding to the negatively charged phosphate groups of LPS, reducing electrostatic repulsion and stabilizing LPS aggregates, potentially leading to a shift in their net charge. These findings highlight the pivotal role of LPS supramolecular structure in modulating FXII activity, providing mechanistic insights into the interplay between bacterial components and the coagulation cascade.