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Biomedical subjects

R Mendelsohn

Publications and source records attributed to R Mendelsohn.

At least 109 records · Page 6Linked to original sources

Raman and Fourier transform infrared spectroscopic studies of the interaction between glycophorin and dimyristoylphosphatidylcholine.

Glycophorin from the human erythrocyte membrane has been isolated in pure form and reconstituted into large unilamellar vesicles with 1,2-dimyristoyl-3-sn-phosphatidylcholine at lipid/protein mole ratios ranging from 50:1 to 200:1. The effect of protein on the phospholipid phase transition has been monitored by Raman and Fourier transform infrared spectroscopy and differential scanning calorimetry. No evidence for an immobilized higher melting lipid component is observed. The gel to liquid-crystalline phas transition is significantly broadened and shifted to lower temperatures as the proportion of protein is increased, while the pretransition is abolished. At all temperatures, the mobility of the acyl chains is increased by the addition of protein while interchain lateral interactions are disrupted. However, there is no evidence for a significant change in the conformational order at low temperatures (approximately 5 degrees C) or ii the liquid-crystalline phase.

Binding Sites↗

Deuterated phospholipids as Raman spectroscopic probes of membrane structure. Phase diagrams for the dipalmitoyl phosphatidylcholine(and its d62 derivative)-dipalmitoyl phosphatidylethanolamine system.

Raman spectroscopic techniques have been used to construct phase diagrams for the binary phospholipid systems, DPPC-d62/DPPE and DPPC/DPPE (DPPC, dipalmitoyl phosphatidylcholine; DPPE, dipalmitoyl phosphatidylethanolamine). For the former, the half-width of the C-2H stretching modes of the deuterated component near 2100 cm-1 serves as an indicator of phospholipids fluidity. The phase behavior is described semi-quantitatively using regular solution theory with the following non-ideality parameters: rho(1)0 = 0.75 kcal/mol and rho(s)0 = 1.05 kcal/mol. The use of deuterated phospholipids as one component of a binary mixture permits direct evaluation of the conformation of a particular component in the mixture throughout the phase separation region. The approach is demonstrated with the help of a simple model correlating the half-width of the symmetric C-2H stretching mode with the fraction of DPPC-d62 hydrocarbon chains in the liquid crystalline state. The effect of chain perdeuteration on the phase behavior of DPPC with DPPE is evaluated by comparison of the phase diagram of the DPPC-d62/DPPE system with that of DPPC-DPPE. The latter has been constructed previously from both probe and calorimetric techniques, and is created from the Raman spectroscopic data using the I(1130/1100) ratio to characterize the transgauche population ratio in non-deuterated hydrocarbon chains. A reasonable fit to the phase behavior is obtained using: rho(1)0 = 0.85 kcal/mol and rho(s)0 = 0.90 kcal/mol. The similarities of the non-ideality parameters in the two phase diagrams indicate that the effect of perdeuteration on the phase behavior of DPPC is not extensive. The use of deuterated phospholipids as essentially unperturbed components of a model membrane system is justified.

Calorimetry, Differential Scanning↗

Lipid-protein interaction in the glycophorin-dipalmitoylphosphatidylcholine system: Raman spectroscopic investigation.

Raman spectra have been recorded as a function of temperature for lipid-protein complexes of glycophorin isolated from erythrocyte membranes reconstituted with dipalmitoylphosphatidylcholine (DPPC) and its chain perdeuterated analogue ([(2)H(62)]DPPC). The conformation of the phospholipid hydrocarbon chains in the vicinity of protein is drastically altered from that in pure lipid dispersions. Analysis of the chain C-(2)H stretching vibrations for complexes of [(2)H(62)]-DPPC-glycophorin shows that at lipid:protein mole ratios of 125:1, a broad melting event occurs that is not observable by calorimetric techniques. The midpoint occurs at temperatures about 15 degrees C below that of the gel/liquid crystal phase transition for [(2)H(62)]DPPC in multilamellar dispersions. The same number of gauche rotamers form in the phospholipid hydrocarbon chains during the melting process as in the phase transition of the unperturbed molecule. Analysis of the C-H stretching region of the Raman spectrum in DPPC-glycophorin complexes indicates that lateral interactions between phospholipid chains in the complex are reduced so that interchain vibrational coupling is minimized. The observed differences between the Raman melting curves and the calorimetric endothermic transitions arise because different populations of phospholipid molecules are sampled in the two experiments. The advantages of Raman spectroscopy for the study of lipid-protein interaction are demonstrated in the current work. Implications for the structure of the lipid in the immediate vicinity of membrane protein are discussed.

Journal Article↗

Zeaxanthin ([3R,3'R]-beta, beta-carotene-3-3'diol) as a resonance Raman and visible absorption probe of membrane structure.

When zeaxanthin ([3R,3R']-beta, beta-carotene-3,3'diol) is inserted into phospholipid dispersions and the latter heated through their gel-liquid crystal phase transitions, large changes are noted in the resonance Raman and absorption spectra of the carotenoid molecule. By analogy with the data of Carey and co-workers (J. Raman Spectrosc. 6:282) who studied the aggregation of zeaxanthin in acetone-water solutions, it is suggested that the carotenoid aggregates in the phospholipid gel state while forming a monomer in liquid crystal phases. The alterations in both the visible absorption and resonance Raman data have been used to monitor phospholipid phase behavior in dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine, (DSPC) one-component systems and binary mixtures. The phase diagram obtained for the binary system, as constructed from visible absorption and resonance Raman data, is compared with that of Shimshick and McConnell (Biochemistry. 12:2351) obtained from electron spin resonance (ESR) studies. Although the agreement between absorption and ESR data is generally satisfactory, onset temperatures for phase separation at low DSPC mole fractions deduced from resonance Raman measurements are several degrees lower than those from the other methods. Nevertheless, the use of zeaxanthin as a resonance Raman and visible absorption probe behavior will be useful in some situations where ordinary Raman spectroscopic data cannot be obtained easily. The advantage of the resonance Raman approach is illustrated in a study of the phase behavior of a phospholipid extract of a cel- mutant of Neurospora crassa. A phase separation region is observed with onset and completion temperatures of -19 and -6 degrees C, respectively.

Carotenoids↗

Use of deuterated phospholipids in Raman spectroscopic studies of membrane structure. I. Multilayers of dimyristoyl phosphatidylcholine (and its -d54 derivative) with distearoyl phosphatidylcholine.

The temperature dependence of the Raman spectrum has been studied for binary phospholipid mixtures of dimyristoyl phosphatidylcholine (and its chain deuterated -d54 derivative) with distearoyl phosphatidylcholine. Two distinct melting regions are observed for the 1 : 1 mole ratio mixture. The use of deuterated phospholipid permits the identification of the lower (approximately 22 degrees C) transition with primarily the melting of the shorter chain component, and the higher (approximately 47 degrees C) transition primarily with the melting of the longer chains. The C-H stretching vibrations of the distearoyl component respond to the melting of the dimyristoyl component, an apparent consequence of alterations in the lateral interactions of the distearoyl chains. These changes in the C-H spectral region suggest that phase separation does not occur in the gel state for this system. The results are in reasonable accord with recent calorimetric studies (Mabrey, S. and Sturtevant, J.M. (1976) Proc. Natl. Acad. Sci. U.S. 73, 3862-3866). The feasibility of using deuterated phospholipids to monitor the conformation of each component in a binary phospholipid mixture is demonstrated.

Chemical Phenomena↗

Length of stay and behavior patterns of hospitalized schizophrenics.

A behavioral observation system, which consists of a series of objectively described behavior categories and an apparatus for recording the duration and frequency of ongoing behaviors in each category, was used to study the behavior on the ward of 21 long-term and 21 short-term matched hospitalized schizophrenics. Results of the study supported the major hypothesis that long-term hospitalized schizophrenics show more withdrawn and inappropriate behaviors and fewer social and appropriate behaviors than short-term hospitalized schizophrenics. Among the short-term patients, those hospitalized from four months to one year showed the most adaptive behaviors and the fewest inappropriate behaviors.

Humans↗

Deuterated fatty acids as Raman spectroscopic probes of membrane structure.

Raman spectra are reported for the C-D stretching region of stearic acid-d35 bound in egg lecithin multilayers. The temperature dependence of the spectra shows that the linewidth of the C-D stretching bands is a sensitive and non-perturbative probe of membrane hydrocarbon chain conformation. The utility of this approach for studying lipid conformation in membranes containing a significant fraction of non-lipid component is discussed.

Deuterium↗

Thermal denaturation and photochemistry of bacteriorhodopsin from Halobacterium cutirubrum as monitored by resonance Raman spectroscopy.

Resonance Raman studies of the thermal denaturation of bacteriorhodopsin from Halobacterium cutirubrum show that the N-retinylidenelysine moiety present in the chromophore is N-protonated. This corroborates an earlier suggestion of Lewis et al. ((1974) Proc. Natl. Acad. Sci. U.S., 71, 4462-4466). The widely differing excitation profiles of two -C=C- stretching modes are explained in terms of the light-initiated reaction cycle in the molecule. Glutaraldehyde fixation of bacteriorhodopsin has no effect on the intensity ratio of the two modes, suggesting that no large motion of the protein is necessary for the photoreaction cycle to occur.

Bacteriorhodopsins↗

The effect of sonication on the hydrocarbon chain conformation in model membrane systems: a Raman spectroscopic study.

Raman spectra are presented for egg lecithin above and below the gelliquid crystal phase transition, and several regions of the Raman spectrum are shown to be sensitive to conformational changes in the hydrocarbon chains. These regions are used to investigate the effect of sonication on the structure of egg lecithin and dipalmitoyl lecithin vesicles. Sonication of both egg lecithin above Tm, and dipalmitoyl lecithin above and below Tm produces no change in the relative population of trans and gauche isomers in any of the systems studied. Sonication does however appear to effect interchain interactions, a possible consequence of imperfect packing towards the center of the bilayers in vesicle systems.

Lasers↗

Raman studies of the C-H and C-D stretching regions in stearic acid and some specifically deuterated derivatives.

Raman spectra of polycrystalline stearic acid-do, stearic acid-d35, 16:16-d2-18:18:18-d3-stearic acid, 18:18:18-d3-stearic acid, 17:17-d2-stearic acid, 17-d1-stearic acid, 16:16-d2-stearic acid, 12:12-d2-stearic acid and 12-d1-stearic acid have been obtained for the region containing the C-D and C-H stretching vibrations. Assignments of the methyl, methyl-d3, methylene, methylene-d2 and methylene-d1 stretching vibrations are discussed.

Deuterium↗

Gathering naturalistic, objective data on the behavior of schizophrenic patients.

A behavioral observation system, consisting of 12 behavior categories and an apparatus for recording them, was designed as a tool for gathering objective, naturalistic data on the ongoing behavior of hospitalized schizophrenics. After the system was tested and evaluated, it was used to draw behavioral profiles of 62 schizophrenics on two psychiatric wards of a Veterans Administration hospital. The results indicate the labeled schizophrenic is typified by a lack of adaptive behavior, a blankness, and a failure to get involved with his environment.

Adaptation, Psychological↗