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  • International Journal of Artificial Organs

Volume 29, Issue 2, February 2006, Pages 239-250

Multi-scale analysis of the Toraymyxin adsorption cartridge part 1: Molecular interaction of polymyxin B with endotoxins

Vesentini, S., Soncini, M., Zaupa, A., Silvestri, V., Fiore, G.B., Redaelli, A.

  • International Journal of Artificial Organs

Volume 29, Issue 2, February 2006, Pages 251-260

Multi-scale analysis of the Toraymyxin adsorption cartridge part II: Computational fluid-dynamic study

Fiore, G.B., Soncini, M., Vesentini, S., Penati, A., Visconti, G., Redaelli, A.

Multi-scale analysis of the Toraymyxin adsorption cartridge part 1: Molecular interaction of polymyxin B with endotoxins
Vesentini, S., Soncini, M. Zaupa, A., Silvestri, V., Fiore, G.B., Redaelli, A.
Abstract

Endotoxins or lipopolysaccharides are the main constituents of the outer leaflet of Gram-negative bacteria membrane and play a central role in the pathogenesis of the septic shock. Polymyxin B has both antibacterial and antiendotoxin capability, indeed it is able to destroy the bacterial outer membrane and bind endotoxin neutralizing its toxic effects. Cartridges containing polymyxin B-immobilized fibers (Toraymyxin PMX-F, Toray Industries, Japan) are used in extracorporeal hemoperfusion to remove circulating endotoxin. The aim of this study is the characterization of the polymyxin B-endotoxin system at the molecular level, thus providing quantitative evaluation of the binding forces exerted in the molecular complex. Polymyxin B was interfaced with five molecular models of lipopolysaccharides differing in their structure and molecular mechanics simulations were performed at different intermolecular distances aimed at calculating the interaction energies of the complex. Binding forces were calculated by fitting interaction energies data. Results show that in the short range the polymyxin B-endotoxin complex is mediated by hydrophobic forces and in the long range the complex is driven by ionic forces only. From a mechanical standpoint, polymyxin B-endotoxin complex is characterized by maximum binding forces ranging between 1.39 nN to 3.79 nN. The knowledge of the binding force behavior at different intermolecular distances allows further investigations at higher scale level (Part II). © Wichtig Editore, 2006.
Author Keywords
Endotoxins; Lipopolysaccharide; Molecular interaction; Molecular modelling; Polymyxin B; Sepsis

Multi-scale analysis of the Toraymyxin adsorption cartridge part II: Computational fluid-dynamic study
Fiore, G.B., Soncini, M., Vesentini, S., Penati, A., Visconti, G., Redaelli, A. Abstract

Extracorporeal endotoxin removal by means of the Toraymyxin device is based on the ability of polymyxin B to bind endotoxins with a high specificity. The endotoxins/polymyxin molecular interactions were computationally analyzed in a parallel work (Part I). In this paper we investigate with a multi-scale approach the phenomena involving blood and plasma fluid dynamics inside the device. The macro- and mesoscale phenomena were studied by means of 3D models using computational fluid dynamics. The flow behavior in the sorbent material was focused, modeling the sorbent as a homogeneous porous medium at the macroscale level, or accounting for the realistic geometry of its knitted fibers at the mesoscale level. A microscale model was then developed to analyze the behavior of endotoxin molecules subjected to the competition of flow drag and molecular attraction by fiber-grafted polymyxin B. The macroscale results showed that a very regular flow field develops in the sorbent, furthermore supplying the peak velocity to be input in the lower-scale model. The mesoscale analysis yielded the realistic range for wall shear stresses (WSSs) acting on fiber walls. With WSS values in the entire range, the results of the microscale analysis demonstrated that the capability of polymyxin B to capture endotoxin molecules from the flow extends at distances one order of magnitude greater than the characteristic distance of the stable intermolecular bond. We conclude that the use of an integrated, multi-scale analysis allows for a comprehensive understanding of the complex mechanisms involved in endotoxin sorption phenomena with immobilized polymyxin B. © Wichtig Editore, 2006.
Author Keywords
Computational fluid dynamics; Endotoxins; Multi-scale modeling; Polymyxin B; Sepsis

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