A MODEL OF HYDROGEN-BOND FORMATION IN PHOSPHATIDYLETHANOLAMINE BILAYERS

We have modelled hydrogen bond formation in phospholipid bilayers form ed, in excess water, from lipids with phosphatidylethanolamine (PE) he adgroups. The hydrogen bonds are formed between the NH3+ group and eit her of the PO2- or the (sn2 chain) C=O groups. We used a model that re presented the conformational states accessible to a PE headgroup by 17 states and modelled lipid dipole-dipole interactions using a non-loca l electrostatics theory to include the effects of hydrogen bonding in the aqueous medium. We used Monte-Carlo simulation to calculate equili brium thermodynamic properties of bilayers in the fluid (T = 340 K) or gel (T = 300 K) phases of the bilayer. We defined E-h to be the diffe rence in free energy between a hydrogen bond formed between a pair of lipid groups, and the energy of hydrogen bonds formed between water an d those two groups, and we required its average value, [E-h], to be si milar to -0.3 kcal/mol (similar to -0.2 x 10(-13) erg) as reported by T.-B. Shin, R. Leventis, J.R. Silvius, Biochemistry 30 (1991) 7491. We found: (i) E-h = -0.9 X 10(-13) erg gave [E-h] = -0.21 X 10(-13) erg (gel phase) and [E-h] = -0.19 X 10(-13) erg (fluid phase). (ii) The re lative number of C=O groups on the sn2 chain calculated to take part i n interlipid hydrogen bonding in the fluid phase compared to the gel i s 1.06 which compares well with the experimental ratio of similar to 1 .25 (R.N.A.H. Lewis, R.N. McElhaney, Biophys. J. 64 (1993) 1081). The ratio of such groups taking part in interlipid hydrogen bonding compar ed to water hydrogen bonding in each phase was calculated to lie betwe en 0.16 and 0.17. (iii) We calculated the distribution of positions of the headgroup moieties: P, O, CH2(alpha), CH2(beta) and N, and found that, in both phases, the O lay furthest from the hydrocarbon chain la yer (average similar to 5.3 Angstrom) with the PO2 and NH3 groups lyin g at similar to 5 Angstrom. This results in the P-N dipole lying nearl y parallel to the bilayer plane in both phases. The thickness of the h eadgroup layer underwent essentially no change on going from the gel t o the fluid phase. The H-2 NMR quadrupole splittings for the alpha and beta CH2 groups were 4.9 and 5.7 kHz (fluid phase) and 7.1 and 7.3 kH z (gel phase), respectively, on the assumption of sufficiently rapid r otation around the z-axis. (iv) In both phases, the location of the NH 3+ group exhibited a strong peak around 5.2 Angstrom into the aqueous medium, with much smaller peaks around 2.6 and 7.8 Angstrom, the two C H2 groups exhibited narrower, double-peaked distributions and the O an d the PO, each exhibited a narrow single peak. (v) PE headgroups, in a homogeneous gel phase, exhibited dipolar orientational long-range ord er in the plane of the bilayer. The distribution of orientation angles exhibited a full width at half height of between similar to 40'' and similar to 50''. In a fluid phase no such order was observed. (vi) The number of hydrogen bonds did not differ substantially between the flu id and get phases. This model is unlikely to display any significant e ffect of hydrogen bonding upon the ''main'' hydrocarbon chain melting phase transition at T-m, except, possibly, a broadening of any hystere sis, compared to the case of PC bilayers where interlipid hydrogen bon ding is absent. (C) 1998 Elsevier Science B.V.