Partition of common anesthetic molecules in the liquid disordered phase domain of a composite multicomponent membrane Anirban Polley References Abstract
Despite a vast clinical application of anesthetics, the molecular level of understanding of general anesthesia is far from our reach. Using atomistic molecular dynamics simulation, we study the effects of common anesthetics: ethanol, chloroform, and methanol in the fully hydrated symmetric multicomponent lipid bilayer membrane comprised of an unsaturated palmitoyl-oleoyl-phosphatidyl-choline (POPC), a saturated palmitoyl-sphingomyelin, and cholesterol, which exhibits phase coexistence of liquid-ordered ( l l d ) phase domains. We find that the mechanical and physical properties such as the thickness and rigidity of the membrane are reduced while the lateral expansion of the membrane is exhibited in the presence of anesthetic molecules. Our simulation shows both lateral and transverse heterogeneity of the anesthetics in the composite multicomponent lipid membrane. Both ethanol and chloroform partition in the POPC-rich l phase domain, while methanol is distributed in both l l d phase domains. Chloroform can penetrate deep into the membrane, while methanol partitions mostly at the water layer closed to the head group and ethanol at the neck of the lipids in the membrane.
Department of Chemical Engineering, Columbia University, New York City, New York 10027, USA Click to Expand Images Figure 1
Snapshot of equilibrium configuration of the symmetric bilayer membranes comprising POPC (gray), PSM (orange), Chol (yellow), and water (cyan) with (a) ethanol (red), (b) chloroform (blue), and (c) methanol (green), respectively. Panel (a) shows that ethanol partitions at the lipid-water interface, whereas chloroform can penetrate anywhere the membrane shown in (b). But, methanol mostly stays in the water to head group of the lipids in the membrane shown in (c).
Electron density of each component vs z axis (normal to membrane) of the symmetric bilayer membrane having ethanol, chloroform, and methanol, respectively are shown in (a)–(c). Reuse & Permissions Figure 3
Spatial number density of each component in the membrane with ethanol, chloroform, and methanol are shown in (a), (b), and (c), respectively [ 39, 51 ]. Reuse & Permissions Figure 5
Spatial heterogeneity of thickness of the ternary symmetric bilayer membrane comprised of POPC, PSM, and Chol without and with ethanol, chloroform, and methanol shown in (a), (b), (c), and (d), respectively [ 39 ]. LUT bar indicates the thickness of the membrane in nm. Reuse & Permissions Figure 6
(a) Deuterium order parameter (S) vs carbon number of the acyl chain of the lipids of the multicomponent symmetric membrane without (black) and with ethanol (red), chloroform (blue), and methanol (green), respectively. (b) The change of deuterium order parameter ( δ s ) vs carbon number of the acyl chain of the lipids in the membrane with anesthetics compared to without anesthetic lipid membrane.