Coarse-Grained Molecular Dynamics Study of Permeability Enhancement in DPPC Bilayers by Incorporation of Lysolipid

Abstract

The enhanced permeability of flat lipid bilayer membranes at their gel to liquid-crystalline (LC) phase transition has been explored using coarse-grained molecular dynamics. The phase transition temperature, T m , is deduced by monitoring the area per lipid, the lipid lateral diffusion constant, and the lipid-lipid radial distribution function. We find that a peak in the permeability coincides with the phase transition from the gel to LC state when lysolipid is present. This peak in permeability correlates with a jump in the area per lipid near the same temperature as well as increased fluctuations in the lipid bilayer free volume. At temperatures above T m , the permeability is only slightly dependent on the amount of lysolipid present. The increased free volume due to the "missing tail" of the lysolipid is partially compensated for by a decrease in area per lipid as the amount of lysolipid increases. We also found that in the coarse-grained model a small amount (≤15 mol %) of lysolipid stabilizes the gel phase and increases the phase transition temperature, while a larger amount of lysolipid (20 mol %) reduces T m back to that for pure DPPC, and bilayers consisting of ≥30 mol % lysolipid did not form a gel phase but still exhibited a peak in permeability near T m for pure DPPC.

Development and modeling of arsenic-trioxide–loaded thermosensitive liposomes for anticancer drug delivery

“…The phase transition can be verified by monitoring the area/lipid, the diffusion coefficient of DPPC, or the radial distribution function as the temperature is changed. For quantitative details of these properties for DPPC/MPPC bilayers, see ref., 33 but here we report the general result that there is a peak in permeability for DPPC/MPPC bilayers near the phase transition temperature similar to what is seen in the experimental work of this paper as well as previous experiments. 22 Figure 11 shows the permeability coefficient of water through the bilayer as a function of temperature for 20 and 50 mol% MPPC as well as for a pure DPPC bilayer.…”

“…A quantitative analysis of the free volume properties of DPPC/MPPC bilayers will be discussed in a forthcoming paper. 33 From the permeability coefficient we can estimate the time for release of the liposome cargo. It is straightforward to show that: 30 $$C_{I}false(tfalse)=C_{I}false(0false)e^{false(-3Pt/Rfalse)}$$ where C I (t) is the concentration of the material inside a liposome of radius R at time t .…”

Perspective on the Martini model

“…Another important area of applications of the Martini model is lipid phase behaviour, requiring both large systems due to the collective nature of phase transitions and long simulation times to observe the critical nucleation events. Examples include the formation of gel phases [80][81][82][83][84][85][86] and inverted hexagonal 26,[87][88][89] and cubic phases, 90,91 or transitions between micelles, bicelles, and vesicles. 28 A snapshot of an inverted cubic phase stabilized by fusion peptides, obtained by Fuhrmans and Marrink 91 using a self-assembly approach, is shown in Fig.…”

Simulation Study of the Permeability of a Model Lipid Membrane at the Fluid–Solid Phase Transition

“…A likely explanation is that the expanded area per lipid in the fluid phase lowers the free energy barrier to permeation in that local area by allowing more free room during the permeation process. 27 Such an effect should be sensitive to the permeant's size. Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Permeant size effect.…”