Perturbation of lipid membrane structure and dynamics induced by doping with alcohol

Beskrivelse

The effect of anaestesia has been known for a very long time, but the reason why anaestesia works is still poorly understood on a molecular level [1-3]. In this context it is discussed in the literature whether the effect of the anaestesia is due to a specific interaction between an anaestetic molecule and a membrane protein, or due to a less specific structural perturbation of the lipid membrane by the anaestetic molecules. Many molecularly different molecules have an anestetic effect and in our investigation we focus on 1-alcohols, which are also interesting from the more physico-chemical perspective of small amphiphilic molecules perturbing the lipid membrane structure.Unilamellar vesicles (ULV's) of 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC), serve in the present investigation as a simple model system for the cell membrane. We have performed structural and thermodynamic investigations of the effect of adding different 1-alcohols to the model system, using small-angle neutron and x-ray scattering (SAXS and SANS) together with differential scanning calorimetry (DSC). In order to elucidate dynamic effects of adding alcohol, inelastic neutron scattering is currently being employed. The structural investigations using SANS have focused on 1-ethanol, 1-butanol, 1-hexanol, 1-octanol, 1-decanol and 1-dodecanol, respectively, which are added to the DMPC ULV's with concentrations in the range of 3 - 10 lipid molecules pr. alcohol molecule in the membrane. Measurements were performed at 30oC, 40oC and 50oC. It is known from densitometry [4] that for the shorter chain alcohols up to 1-hexanol, the alcohols pack more loosely into the membrane compared to the pure state, while the longer chain alcohols pack more effectively in the membrane than in the pure state. This is consistent with molecular dynamics simulations on 1-hexanol in DMPC bilayers [5] showing that while the packing density in the outer interfacial part of the membrane remains constant when hexanol is added, the packing density in the interior of the membrane is becoming looser and this part of the bilayer is thinned leading to an overall thinning of the membrane. Our SANS measurements [6] are consistent with these findings, showing that adding hexanol and octanol leads to a thinning of the bilayer which increases with the alcohol concentration, while the longer chain alcohols leads to a thickening of the membrane. For these longer chain alcohols the mismatch between alcohol and lipid chain length is of less significance while the lipid acyl chains are stretched next to the alcohol chains thus resulting in an overall thickening of the membrane.

[1] B. Antkowiak, Naturwissenschaften, 2001, Vol. 88, pp. 201- 213

[2] R.S. Cantor, Biochemistry, 1997, Vol. 36, pp. 2339-2344.

[3] T. Heimburg and A. D. Jackson, Biophysical Journal, 2007, Vol. 92, pp. 3159-3165

[4] T. H. Aagaard, M. N. Kristensen, P. Westh, Biophysical Chemistry, 2006, Vol. 119, pp. 61 - 68

[5] U.R. Petersen, G.H. Peters and P. Westh, Biophysical Chemistry, 2007, Vol. 125, pp. 104-111

[6] D. Posselt, A. Lund, P. Westh and L. Arleth, in preparation