Alamethicin in lipid bilayers: Combined use of X-ray scattering and MD Simulations
Biochimica et Biophysica Acta 1788 (2009), 1387–1397
Jianjun Pan1, D. Peter Tieleman2, John F. Nagle1,3, Norbert Kučerka1,4 and Stephanie Tristram-Nagle1
1Biological Physics Group, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA 2Department of Biological Sciences, University of Calgary, Calgary, AB, Canada 3Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA 4Canadian Neutron Beam Centre, National Research Council, Chalk River, Ontario K0J1J0, Canada
a b s t r a c t We study fully hydrated bilayers of two di-monounsaturated phospholipids diC18:1PC (DOPC) and diC22:1PC with varying amounts of alamethicin (Alm). We combine the use of X-ray diffuse scattering and molecular dynamics simulations to determine the orientation of alamethicin in model lipids. Comparison of the experimental and simulated form factors shows that Alm helices are inserted
trans- membrane at high humidity and high concentrations, in agreement with earlier results. The X-ray
scattering data and the MD simulations agree that membrane thickness changes very little up to 1/10 Alm/DOPC. In contrast, the X-ray data indicate that the thicker diC22:1PC membrane thins with added Alm, a total decrease in thickness of 4 Å at 1/10 Alm/diC22:1PC. The different effect of Alm on the thickness changes of the two bilayers is consistent with Alm having a hydrophobic thickness close to the hydrophobic thickness of 27 Å for DOPC; Alm is then mismatched with the 7 Å thicker diC22:1PC bilayer. The X-ray data indicate that Alm decreases the bending modulus (Kc) by a factor of ~2 in DOPC and a factor of ~10 in diC22:1PC
membranes (P/L~1/10). The van der Waals and fluctuational interactions between bilayers are also evaluated through determination of the anisotropic B compressibility modulus.