Abstract
Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid bilayers predicted the existence of three regimes of action of DMSO: membrane loosening, pore formation and bilayer collapse. We show here that these modes of action are also reproduced in the presence of cholesterol in the bilayer, and we provide a description at the atomic detail of the DMSO-mediated process of pore formation in cholesterol-containing lipid membranes. We also successfully explore the applicability of DMSO to promote plasma membrane permeability to water, calcium ions (Ca2+) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes. The experimental results on cells in culture can be easily explained according to the three expected regimes: in the presence of low doses of DMSO, the membrane of the cells exhibits undulations but no permeability increase can be detected, while at intermediate DMSO concentrations cells are permeabilized to water and calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be associated to the MD-predicted consequences of the effects of the DMSO at low and intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced membrane-destructuring effects described in the MD simulations.
Highlights
Dimethyl sulfoxide (DMSO, (CH3)2SO) is a small amphiphilic molecule that is traditionally used as a cryoprotectant [1], solvent for peptides in NMR studies [2], cell fusogen [3], and chemical penetration enhancer to deliver active molecules through the skin and into the cells [4]
In this paper we report the main observations from Molecular dynamics (MD) simulations of Chol-containing dioleoylphosphatidylcholine (DOPC) bilayers under the influence of DMSO
MD Simulations are run for DOPC membrane systems mixed with 20 mol% of Chol and different molar fractions of DMSO in the solvent mixture
Summary
Dimethyl sulfoxide (DMSO, (CH3)2SO) is a small amphiphilic molecule that is traditionally used as a cryoprotectant [1], solvent for peptides in NMR studies [2], cell fusogen [3], and chemical penetration enhancer to deliver active molecules through the skin and into the cells [4]. Experimental studies devoted to the investigation of the specific changes of lipid in membranes in the presence of DMSO have revealed that this compound replaces water in the inner region of the lipid headgroup [5] and causes an increase of area per lipid and a decrease of membrane thickness [6]. These effects have been confirmed by means of Molecular dynamics (MD) simulations in a series of recent articles. Anwar et al showed a DMSOmediated enhancement of the permeability through the formation of water pores, both in atomistic [9,10] and coarse-grained [11] MD simulations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
