Myer Bloom

Quadrupolar echo deuteron magnetic resonance spectroscopy in ordered hydrocarbon chains

Abstract The quadrupolar spin echo from deuterons in ordered hydrocarbon systems is shown to provide a much more reliable spectrum than the conventional free induction decay Fourier transform. Spectrometer dead time is eliminated, phase correction uncertainties removed and signal/noise enhanced.

Physical properties of the fluid lipid-bilayer component of cell membranes : a perspective

The motivation for this review arises from the conviction that, as a result of the mass of experimental data and observations collected in recent years, the study of the physical properties of membranes is now entering a new stage of development. More and more, experiments are being designed to answer specific, detailed questions about membranes which will lead to a quantitative understanding of the way in which the physical properties of membranes are related to and influence their biological function.

Mattress model of lipid-protein interactions in membranes.

A thermodynamic model is proposed for describing phase diagrams of mixtures of lipid bilayers and amphiphilic proteins or polypeptides in water solution. The basic geometrical variables of the model are the thickness of the hydrophobic region of the lipid bilayer and the length of the hydrophobic region of the proteins. The model incorporates the elastic properties of the lipid bilayer and the proteins, as well as indirect and direct lipid-protein interactions expressed in terms of the geometrical variables. The concept of mismatch of the hydrophobic regions of the lipids and proteins is an important ingredient of the model. The general phase behavior is calculated using simple real solution theory. The phase behavior turns out to be quite rich and is used to discuss previous experiments on planar aggregations of proteins in phospholipid bilayers and to propose a systematic study of synthetic amphiphilic polypeptides in bilayers of different thicknesses. The model is used to interpret the influence of the lipid-protein interaction on calorimetric measurements and on local orientational order as determined by deuterium nuclear magnetic resonance.

De-pake-ing of NMR spectra

A procedure suggested elsewhere (Bloom, Davis, and MacKay, Chem. Phys. Lett.80, 198 (1981)) for extracting the nuclear magnetic resonance spectrum of an oriented system from the spectrum consisting of a superposition of contributions from randomly oriented domains (“powder spectrum”) is modified to enable its application to a wider range of systems. The method works well for the spectra associated with quadrupolar, dipolar, and anisotropic chemical or Knight shift interactions whose secular components have axial symmetry and scale as 3 cos2 θ − 1, where θ is the angle between the symmetry axis and the external magnetic field. Simulated spectra are used to explore the applicability of the method to lineshapes with different types of broadening and to lineshapes arising from nonaxially symmetric systems.

Direct determination of the oriented sample nmr spectrum from the powder spectrum for systems with local axial symmetry

Abstract A procedure is described for extracting the nuclear magnetic resonance spectrum of an oriented system from the spectrum of a superposition of randomly oriented domains. The procedure is applicable to dipolar, quadrupolar and anisotropic chemical shift interactions in systems having local axial symmetry and is illustrated using simulated and experimental spectra.

From Lanosterol to Cholesterol: Structural Evolution and Differential Effects on Lipid Bilayers

Cholesterol is an important molecular component of the plasma membranes of mammalian cells. Its precursor in the sterol biosynthetic pathway, lanosterol, has been argued by Konrad Bloch (Bloch, K. 1965. Science. 150:19-28; 1983. CRC Crit. Rev. Biochem. 14:47-92; 1994. Blonds in Venetian Paintings, the Nine-Banded Armadillo, and Other Essays in Biochemistry. Yale University Press, New Haven, CT.) to also be a precursor in the molecular evolution of cholesterol. We present a comparative study of the effects of cholesterol and lanosterol on molecular conformational order and phase equilibria of lipid-bilayer membranes. By using deuterium NMR spectroscopy on multilamellar lipid-sterol systems in combination with Monte Carlo simulations of microscopic models of lipid-sterol interactions, we demonstrate that the evolution in the molecular chemistry from lanosterol to cholesterol is manifested in the model lipid-sterol membranes by an increase in the ability of the sterols to promote and stabilize a particular membrane phase, the liquid-ordered phase, and to induce collective order in the acyl-chain conformations of lipid molecules. We also discuss the biological relevance of our results, in particular in the context of membrane domains and rafts.

Smoothed orientational order profile of lipid bilayers by 2H−nuclear magnetic resonance

A new method has been developed to determine the complete orientational order profile of lipid bilayers using 2H-NMR. The profile is obtained from a single powder spectrum of a lipid which has a saturated chain fully deuteriated. The smoothed order profile is determined directly from the normalized dePaked spectrum assuming a monotonic decrease of the order along the acyl chain. The oscillatory variations of the order at the beginning of the chain are not described by this method. However the smoothed order profile reveals in a straightforward way the crucial features of the anisotropic order of the bilayer.

Spin Echoes and Chemical Exchange

The amplitude of the nuclear induction signal is calculated for pulsed nuclear magnetic resonance experiments for systems in which chemical exchange takes place between two sites of different Larmor frequency. General expressions are given, within the scope of first order rate theory for one and two pulse experiments as well as multiple pulse (Carr—Purcell) sequences. It is proven that for a Carr—Purcell sequence the decay is always expressible as a sum of two exponentials. The two time constants are derived for the general case and some special cases are discussed in detail. The theory makes possible the measurement of exchange rate constants using spin‐echo techniques without the use of computers and seems relatively easy to generalize to more complicated systems.

Modulation of the orientational order profile of the lipid acyl chain in the Lα phase

The orientational order profile along the lipid acyl chain has been characterized under several different conditions of polar headgroup composition, temperature, and cholesterol content. Despite the different nature of these factors, the variation of the order is governed by two common trends. First, the relative change of order induced by the variation of these factors is always more pronounced towards the end of the chain than for the methylene groups near the interface. Second, there is, to a first approximation, a distinct correlation between the magnitude of the order parameters and the shape of the order profile. For example when the chain is highly ordered, the relative width of the order distribution is narrow indicating that the plateau region is longer. These conclusions suggest that the orientational order profile depends on only a small number of parameters and demonstrate clearly that the correlation length for changes in orientational order is much greater than one C-C bond length. Our results also show that the reduced temperature is not related in simple terms to orientational order and probably has little theoretical significance. The orientational order profiles of POPC and POPE bilayers are significantly different even when expressed in terms of reduced temperature. The behavior of POPC/cholesterol systems also indicates that the orientational order of the lipid chain and the gel-to-liquid crystalline phase transition temperature are not related in a straightforward manner.

Dynamic properties of the backbone of an integral membrane polypeptide measured by 2H-NMR

The 2H-NMR spectrum of the exchangeable hydrogens of the synthetic amphiphilic polypeptide, lys2-gly-leu24-lys2-ala-amide, was measured for the solid peptide at room temperature and, as a function of temperature, for the peptide incorporated into hydrated dipalmitoylphosphatidylcholine (DPPC) bilayers. This study is a prototype of a similar class of experiments which can be carried out on integral membrane proteins to characterize, quantitatively, the dynamic properties of integral membrane proteins. At temperatures below the DPPC gel-liquid crystalline phase transition, the 2H NMR spectrum was very similar to that of the solid peptide indicating that the peptide was immobilized in the lipid bilayer on the time scale (≈10-5 s) of the 2H-NMR measurements. The 2H-NMR spectrum above the phase transition corresponded to that expected from a peptide in the α-helical conformation reorienting rapidly about the symmetry axis of the α-helix. Measurements of the quadrupolar echo relaxation time, T2e, gave a quantitative measure of the correlation time, τc, for this motion. The value of τc decreased rapidly with increasing temperature as the fraction of DPPC molecules in the liquid crystalline phase increased, reaching a value of 2×10-7s above the phase transition. The observation of a characteristic minimum in T2e as the temperature was raised provided a definitive, quantitative interpretation of the T2e measurements. Using the known geometry of the peptide and the theory of uniaxial rotational diffusion, a value of η=1.1 poise was obtained for the effective viscosity of the membrane in close agreement with values obtained previously from transient linear dichroism measurements.