Model studies of lipid flip-flop in membranes

  • Giulia Parisio
  • Alberta Ferrarini
  • Maria Maddalena Sperotto
Article

Abstract

Biomembranes, which are made of a lipid bilayer matrix where proteins are embedded or attached, constitute a physical barrier for cell and its internal organelles. With regard to the distribution of their molecular components, biomembranes are both laterally heterogeneous and transversally asymmetric, and because of this they are sites of vital biochemical activities. Lipids may translocate from one leaflet of the bilayer to the opposite either spontaneously or facilitated by proteins, hence they contribute to the regulation of membrane asymmetry on which cell functioning, differentiation, and growth heavily depend. Such transverse motion—commonly called flip-flop—has been studied both experimentally and computationally. Experimental investigations face difficulties related to time-scales and probe-induced membrane perturbation issues. Molecular dynamics simulations play an important role for the molecular-level understanding of flip-flop. In this review we present a summary of the state of the art of computational studies of spontaneous flip-flop of phospholipids, sterols and fatty acids. Also, we highlight critical issues and strategies that have been developed to solve them, and what remains to be solved.

Keywords

Flip-flop Molecular dynamics simulations Potential of mean force Sterols Fatty acids Phospholipids 

Abbreviations

CG

Coarse grained

DAPC

1,2-Diarachidonoyl-sn-glycero-3-phosphocholine

diC14:1-PC

1,2-Dimyristelaidoyl-sn-glycero-3-phosphocholine

diC18:2-PC

1,2-Dilinoleoyl-sn-glycero-3-phosphocholine

diC22:1-PC

1,2-Dierucoyl-sn-glycero-3-phosphocholine (DEPC)

DLPC

1,2-Dilauroyl-sn-glycero-3-phosphocholine

DMPC

1,2-Dimyristoyl-sn-glycero-3-phosphocholine

DOPC

1,2-Dioleoyl-sn-glycero-3-phosphocholine

DOPG

1,2-Dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)

DOPS

1,2-Dioleoyl-sn-glycero-3-phospho-l-serine

DPD

Dissipative particle dynamics

DPPC

1,2-Dipalmitoyl-sn-glycero-3-phosphocholine

DSPC

1,2-Distearoyl-sn-glycero-3-phosphocholine

DSPS

1,2-Distearoyl-sn-glycero-3-phospho-l-serine

DTPC

1,2-Tetracosatetraenoyl-sn-glycero-3-phosphocholine

MD

Molecular dynamics

PMF

Potential of mean force

POPC

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine

PSM

N-palmitoyl-d-erythro-sphingosylphosphorylcholine

SAPC

1-Stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine

TPS

Transition path sampling

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© Indian Institute of Technology Madras 2016

Authors and Affiliations

  • Giulia Parisio
    • 1
  • Alberta Ferrarini
    • 1
  • Maria Maddalena Sperotto
    • 2
  1. 1.Department of Chemical SciencesUniversity of PadovaPadovaItaly
  2. 2.Center for Biological Sequence Analysis, Department of Systems BiologyTechnical University of DenmarkKgs. LyngbyDenmark

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