Chloroform alters interleaflet coupling in lipid bilayers: an entropic mechanism

Abstract

The interaction of the two leaflets of the plasmatic cell membrane is conjectured to play an important role in many cell processes. Experimental and computational studies have investigated the mechanisms that modulate the interaction between the two membrane leaflets. Here, by means of coarsegrained molecular dynamics simulations, we show that the addition of a small and polar compound such as chloroform alters interleaflet coupling by promoting domain registration. This is interpreted in terms of an entropic gain that would favour frequent chloroform commuting between the two leaflets. The implication of this effect is discussed in relation to the general anaesthetic action.

Effects of fullerene on lipid bilayers displaying different liquid ordering: a coarse-grained molecular dynamics study

“…The difference between the two simulated raft systems is related to the correlation between membrane leaflets. As it was already shown in previous CG MD simulations [34,39], the membrane containing the longesttail lipid (DSPC) shows a clear phase antiregistration behavior (lo and ld are not aligned in the two leaflets), whereas the membrane containing DPPC displays an alignment of the segregating domains (phase registration).…”

“…Because each Voronoi polygon is associated with an individual molecule, lateral (in the same leaflet) and transversal (in opposite leaflets) neighbors can be readily assigned to each membrane molecule. The lo/ld segregation process is quantitatively tracked by means of a segregation parameter  that corresponds to the fraction of lateral contacts between lipid molecules corresponding to the same phase [34]. DUPC molecules are considered to form the ld phase, whereas the saturated PC species correspond to the lo phase.…”

“…The free energy profiles (potential of mean force, PMF) for a fullerene molecule traversing the simulated lipid bilayers are calculated using the umbrella sampling method [37] Visual inspection of the equilibration process before fullerene addition reveals a clear phase segregation process for the two simulated ternary membranes: the saturated lipid forms a packed lipid phase (lo) together with Chol molecules, segregated from a disordered phase (ld) rich in the unsaturated lipid (DUPC) [34]. The difference between the two simulated raft systems is related to the correlation between membrane leaflets.…”

Effects of passive phospholipid flip-flop and asymmetric external fields on bilayer phase equilibria

“…1A is motivated by the following considerations: R minima are lower than AR so that registration is equilibrium; R-R-AR coexistence is possible [4]; AR minima exist to support AR-AR coexistence [8,37,51]. We note that the requirement for the off-diagonal (oval) µ t = µ b contour lines to exist in Fig.…”

“…In model bilayer membranes, phospholipids passively "flip-flop" between the leaflets over minutes, hours or days [3][4][5][6][7], in contrast to the much faster translocation of cholesterol or small-molecule additives [8]. Membranes of living cells use active, ATP-consuming enzymes to move lipids between leaflets [9,10], but also rely on passive flip-flop via, for example, calcium-activated scramblase proteins that allow for rapid inter-leaflet diffusion [11][12][13].…”