Michael F Brown

Abstract:

Based on a previous, more approximate treatment [M. F. Brown, J. Magn. Reson. 35, 203 (1979)], expressions are derived for the quadrupolar spin-lattice (T1) relaxation rates of ²H and ¹⁴N in lipid bilayers. Results are presented for the most general, anisotropic rotational diffusion model describing the segmental or molecular reorientation in lipid bilayers, and the analysis is extended to include relatively slow fluctuations of the local director with respect to the macroscopic bilayer normal. Numerically computed values of T1 for the diffusion model suggest that, even for extremes of ordering and motional anisotropy, such a model cannot by itself quantitatively account for the observed ²H T1 values of multilamellar dispersions of 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), in the liquid crystalline state, as a function of temperature and frequency. The contribution from relatively low frequency motions is modeled in terms either (i) a simple noncollective model in which the slow motions are described in terms of a single effective correlation time, or (ii) a collective model in which the relatively slow reorientation is described by a distribution of correlation times, corresponding to collective fluctuations of the instantaneous director. The experimentally observed dependence of the ²H T1 relaxation rates on the acyl chain segmental order parameter SCD and the resonance frequency ω0 are most consistent with a collective model for slow molecular reorientations in lipid bilayers. The ²H T1 data for the saturated DPPC bilayer, in the liquid crystalline state, can be quantitatively described by a relaxation law of the form T1^-1 = Aτf + BSCD² ω0^-1/2 as observed for simpler nematic and smectic liquid crystals. The first (A) term is suggested to correspond primarily to trans-gauche isomerizations of the lipid acyl chains, while the (B) term describes collective bilayer modes which predominantly influence the frequency dependence of the relaxation. In contrast to earlier conclusions [M. F. Brown et al., J. Chem. Phys. 70, 5045 (1979)], the dominant contribution to the ²H T1 relaxation rates of the saturated DPPC bilayer may arise from collective order fluctuations rather than fast local motions. The value of τf∼10^-11 s obtained by extrapolating T1^-1 to infinite frequency or zero ordering is consistent with the correlation times calculated from ²H or ¹³C T1 data for n-alkanes of equivalent chain lengths, suggesting that the microviscosity of the bilayer hydrocarbon region is not appreciably different from that of paraffinic liquids. © 1982 American Institute of Physics.

PMID: 21806916;PMCID: PMC3145276;Abstract:

We have performed quantum mechanical calculations for retinal model compounds to establish the rotational energy barriers for the C5-, C9-, and C13-methyl groups known to play an essential role in rhodopsin activation. Intraretinal steric interactions as well as electronic effects lower the rotational barriers of both the C9- and C13-methyl groups, consistent with experimental ²H NMR data. Each retinal methyl group has a unique rotational behavior which must be treated individually. These results are highly relevant for the parameterization of molecular mechanics force fields which form the basis of molecular dynamics simulations of retinal proteins such as rhodopsin. © 2011 Biophysical Society.

X-ray and magnetic resonance approaches, though central to studies of G protein-coupled receptor (GPCR)-mediated signaling, cannot address GPCR protein dynamics or plasticity. Here we show that solid-state (2)H NMR relaxation elucidates picosecond-to-nanosecond-timescale motions of the retinal ligand that influence larger-scale functional dynamics of rhodopsin in membranes. We propose a multiscale activation mechanism whereby retinal initiates collective helix fluctuations in the meta I-meta II equilibrium on the microsecond-to-millisecond timescale.

PMID: 11741426;Abstract:

Polyunsaturated lipids in cellular membranes are known to play key roles in such diverse biological processes as vision, neuronal signaling, and apoptosis. One hypothesis is that polyunsaturated lipids are involved in second messenger functions in biological signaling. Another current hypothesis affirms that the functional role of polyunsaturated lipids relies on their ability to modulate physical properties of the lipid bilayer. The present research has employed solid-state ²H NMR spectroscopy to acquire knowledge of the molecular organization and material properties of polyunsaturated lipid bilayers: We report measurements for a homologous series of mixed-chain phosphatidylcholines containing a perdeuterated, saturated acyl chain (n:0) at the sn-1 position, adjacent to docosahexaenoic acid (DHA, 22:6ω3) at the sn-2 position. Measurements have been performed on fluid (Lα)-state multilamellar dispersions as a function of temperature for saturated acyl chain lengths of n = 12, 14, 16, and 18 carbons. The saturated sn-1 chains are therefore used as an intrinsic probe with site-specific resolution of the polyunsaturated bilayer structure. The ²H NMR order parameters as a function of acyl position (order profiles) have been analyzed using a mean-torque potential model for the chain segments; and the results are discussed in comparison with the homologous series of disaturated lipid bilayers. At a given absolute temperature, as the sn-1 acyl length adjacent to the sn-2 DHA chain is greater, the order of the initial chain segments increases, whereas that of the end segments decreases, in marked contrast with the corresponding disaturated series. For the latter, the order of the end segments is practically constant with acyl length, thus revealing a universal chain packing profile. We find that the DHA-containing series, while more complex, is still characterized by a universal chain packing profile, which is shifted relative to the homologous saturated series. Moreover, we show how introduction of DHA chains translates the order profile along the saturated chains, making more disordered states accessible within the bilayer central region. As a result, the area per lipid headgroup is increased as compared to disaturated bilayers. The systematic analysis of the ²H NMR data provides a basis for studies of lipid interactions with integral membrane proteins, for instance in relation to characteristic biological functions of highly unsaturated lipid membranes.