Chemically induced phospholipid translocation across biological membranes.
Chemical means of manipulating the distribution of lipids across biological membranes is of considerable interest for many biomedical applications as a characteristic lipid distribution is vital for numerous cellular functions. Here we employ atomic-scale molecular simulations to shed light on the ability of certain amphiphilic compounds to promote lipid translocation (flip-flops) across membranes. We show that chemically induced lipid flip-flops are most likely pore-mediated: the actual flip-flop event is a very fast process (time scales of tens of nanoseconds) once a transient water defect has been induced by the amphiphilic chemical (dimethylsulfoxide in this instance). Our findings are consistent with available experimental observations and further emphasize the importance of transient membrane defects for chemical control of lipid distribution across cell membranes.
Gurtovenko
Andrey A
AA
Computational Biophysics Laboratory, Institute of Pharmaceutical Innovation, University of Bradford, Bradford, BD7 1DP, U.K.
Onike
Olajide I
OI
Anwar
Jamshed
J
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D001692:Biological Transport; D001703:Biophysics / Q000379:methods*; D002462:Cell Membrane / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008566:Membranes / Q000737:chemistry*; D008968:Molecular Conformation; D010743:Phospholipids / Q000737:chemistry*; D021381:Protein Transport; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
D008051:Lipid Bilayers; D008055:Lipids; D010743:Phospholipids; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D004121:Dimethyl Sulfoxide