USE OF A COMPREHENSIVE APPROACH TO MOLECULAR-DYNAMICS IN ORDERED LIPID SYSTEMS - CHOLESTEROL REORIENTATION IN ORIENTED LIPID BILAYERS - A H-2 NMR RELAXATION CASE-STUDY

In ordered molecular systems, anisotropic deuterium (2H) spin-lattice relaxation affords a method of identifying motional modes with rates on the time scale of the Larmor frequency. Such information augments significantly the more usual temperature- and frequency-dependence relaxation studies. In order to demonstrate the potential of using the specific characteristics of anisotropic 2H relaxation to elucidate details of molecular dynamics in lipid bilayers, cholesterol reorientation in bilayers of dipalmitoylphosphatidylcholine (1:1 mole ratio) was investigated. The present study demonstrates that while anisotropic T1, behavior (β-dependence) can be observed in partially relaxed line shapes of unoriented dispersions in the absence of orientational averaging, a distinct advantage of oriented systems is that they circumvent any orientational-averaging effects of rapid lateral diffusion over the curved liposomal surfaces, a physical process that would thwart any attempt to observe anisotropic relaxation in powder samples. The fused rings of cholesterol present a rigid moiety whose molecular reorientation will relax 2H nucleiat different sites at rates modulated only by the respective angles (θ) between the C-2H bond and the motional averaging axis This fact is exploited to test two simple but fundamentally disparate models for cholesterol dynamics in lipid bilayers, since a correct description of this system shouldsimultaneously predict the anisotropic (β-dependence) relaxation behavior for all labeled sites on the steroid ring system. Simulations of the angular-dependent profiles of both spin-lattice relaxation times (T1(β), T1Q(β)), together with the observed temperature dependence, establish that cholesterol reorients by random 3-fold jumps (large-angle motion) rather than by rotational diffusion (small-angle motion). This study shows the necessity of examining the complete relaxation profile, since monitoring only the extremes (β = 0°, β = 90°) may be insufficient to differentiate between possible motional models. © 1990, American Chemical Society. All rights reserved.