Biomembrane Solubilization Mechanism by Triton X-100: A Computational Study of The Three Stage Model

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Antonio Pizzirusso , Antonio De Nicola , Agur Sevink , Andrea Correa , Michele Cascella , Toshihiro Kawakatsu , mattia rocco , Ying Zhao , Massimo Celino and Giuseppe Milano

Received 9th June 2017 , Accepted 6th September 2017

First published on 6th September 2017

The solubilization mechanism of lipid membrane in presence of Triton X-100 (TX-100) is investigated at molecular resolution by Molecular Dynamics (MD) simulations. Thanks to the large time and length scales accessible by the hybrid particle-field formulation of the models here employed, the complex process of membrane solubilization has been studied, with the goal of verifying the literature Three Stage Model. DPPC lipid bilayers and vesicles have been studied at different concentration of TX-100 detergent employing Coarse Grained (CG) models. Systems up to ~ 600.000 beads, corresponding to more than 2 millions of heavy atoms, have been simulated. Moreover, in order to clarify several experimental evidences, both slow and fast detergent partitions scenarios have been investigated. Flat and curved (vesicles) lipid bilayers surfaces, interacting with TX-100, have been considered to study the curvature effects on the detergent partition rate in the membrane. Shape and conformational changes of mixed DPPC/TX-100 vesicles, as a function of TX 100 content, have also been studied. In particular, high curvature surfaces, corresponding to higher local TX-100 content, promotes a membrane rupture. In flat lipid surfaces, on the time scale simulated the detergent partition is almost absent, following a different pathway of the solubilization membrane mechanism.