title: Ion transport through chemically induced pores in protein-free phospholipid membranes.
abstract: We address the possibility of being able to induce the trafficking of salt ions and other solutes across cell membranes without the use of specific protein-based transporters or pumps. On the basis of realistic atomic-scale molecular dynamics simulations, we demonstrate that transmembrane ionic leakage can be initiated by chemical means, in this instance through addition of dimethyl sulfoxide (DMSO), a solvent widely used in cell biology. Our results provide compelling evidence that the small amphiphilic solute DMSO is able to induce transient defects (water pores) in membranes and to promote a subsequent diffusive pore-mediated transport of salt ions. The findings are consistent with available experimental data and offer a molecular-level explanation for the experimentally observed activities of DMSO solvent as an efficient penetration enhancer and a cryoprotectant, as well as an analgesic. Our findings suggest that transient pore formation by chemical means could emerge as an important general principle for therapeutics.
authors.affiliation: Computational Laboratory, Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Gurtovenko
authors.forename: Jamshed
authors.initials: J
authors.lastname: Anwar
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011189:Potassium Chloride / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine; D012965:Sodium Chloride; D011189:Potassium Chloride; D004121:Dimethyl Sulfoxide