Effects of Alkyl Chain Asymmetry and Cholesterol on the Structural and Mechanical Properties of the Ion Pair Amphiphile Bilayers – A Molecular Dynamics Study

Abstract

Vesicle is a hollow spherical structure with bilayered shell(s) self-assembled from amphiphilic molecules in the aqueous phase Liposomes vesicles fabricated from phospholipids have great potentials in various pharmaceutical fields such as drug or DNA deliveries Yet the high production costs of liposomes has hindered their practical applications Ion pair amphiphile (IPA) a molecular complex composed of two oppositely charged surfactants is structurally similar to a phospholipid and has been proposed as the cheaper lipid substitute However the IPA vesicles exhibit low colloidal stability in general which limits their further application development Reports have shown that the colloidal stability of IPA vesicles can be significantly enhanced via the addition of cholesterol but the detailed stabilization mechanisms remain illusive Furthermore various studies have also suggested different roles for the cationic and anionic component within IPA membrane In this work we utilized molecular dynamics (MD) simulation to study how the cholesterol addition and the IPA chain arrangement affect the properties of IPA-Chol bilayer membrane We focused on the gel-state IPA bilayers composed of one of the two IPAs with the reversed chain arrangements hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium-hexadecylsulfate (DTMA-HS) With increased cholesterol mole fraction (Xchol) the inter-complex spacing between IPAs increases while the alkyl chain ordering decreases consistent with the cholesterol effects on the gel-state phospholipid bilayer Upon the addition of cholesterol the two asymmetric-IPA bilayers show different membrane characteristics including alkyl chain ordering atom mismatching and mechanical moduli The DTMA-HS-Chol systems where the alkyl chain is longer for the anionic component exhibit overall lower chain ordering and smaller mechanical strengths than the HTMA-DS-Chol systems Due to the more disordered alkyl chain DTMA-HS bilayer has higher water permeability than HTMA-DS system Addition of cholesterol reduces the overall water permeability for both IPA systems with the minimum at Xchol = 0 375 The difference between two IPA bilayers is mainly originated from the interplay between the effects of IPA alkyl chain asymmetry and the biased interaction between cholesterol and the anionic surfactant The presented results provide valuable molecular insights into the IPA-Chol mixtures and will be helpful for future IPA designs in various applications in the future

Date of Award	2016 Feb 4
Original language	English
Supervisor	Chi-cheng Chiu (Supervisor)