Biophysical Society Thematic Meeting - October 13-15, 2015

Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling

Poster Abstracts

10-POS Board 10 Amphiphilic Derivatives of Chitosan Hold Similarities with Antimicrobial Peptides in Their Mechanism of Action Fabio D. Nasário 1 , Marcio J. Tiera 1 , Laiz C. Silva-Gonçalves 2 , Vera A. Tiera 1 , Manoel Arcisio- Miranda 2 , Marcia P. Dos Santos Cabrera 1 . 1 Universidade Estadual Paulista - UNESP, São José do Rio Preto, Brazil, 2 Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil. Chitosans have been modified and functionalized to improve their action as antimicrobials. Antimicrobial chitosans may target the phospholipid matrix of cell membranes and this has been considered a target towards which resistance is hardly developed. In this work two chitosan derivatives were designed to gain hydrophobic and cationic character at different ratios. They were synthesized and evaluated for their features as amphiphilic compounds and for their interaction with three model membranes of different lipid composition, mimicking bacterial, fungal and erythrocyte membranes. Antimicrobial and cytotoxic activity was also assessed, demonstrating that both derivatives present antimicrobial activity but just the one with higher cationic character showed cytotoxicity towards human cervical carcinoma cells. The strategy used provided chitosan derivatives with intense lytic activity, inducing more than 70% dye leakage and similar behavior for both derivatives in the anionic model membranes. The less charged compound exhibits a slightly improved selectivity in relation to the anionic over the zwitterionic bilayers. This effect indicates that it is possible to balance the hydrophobic/hydrophilic character to improve the efficiency of chitosan derivatives. The disturbance of the lipid acyl chain order was also observed, and together with zeta potential measurements we hypothesize that the “charge cluster mechanism” ascribed to some antimicrobial peptides could be applied to these chitosan derivatives.

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