Lower Membrane Fluidity Research Articles

Excess membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity

Background & Aims: The relationship between muscle contractility, plasma membrane cholesterol, and fluidity was investigated in human gallbladders with gallstones. Methods: Isolated gallbladder muscle cells were used to measure contraction. Plasma membranes of gallbladder muscle were purified in a sucrose gradient and measured for cholesterol content and cholesterol/phospholipid mole ratio. Membrane fluidity was determined by using fluorescence polarization and was expressed as the reciprocal of anisotropy. Results: The maximal contraction induced by cholecystokinin octapeptide was significantly less in gallbladders with cholesterol stones than in those with pigment stones. The membrane cholesterol content and cholesterol/phospholipid mole ratio were significantly higher in gallbladders with cholesterol stones than in those with pigment stones. Membrane anisotropy was also higher than in gallbladders with pigment stones, reflecting lower membrane fluidity in gallbladders with cholesterol stones. After muscle cells from cholesterol stone gallbladders were incubated with cholesterol-free liposomes for 4 hours, cholecystokinin octapeptide–induced contraction, membrane cholesterol content and cholesterol/phospholipid ratio, and membrane fluidity returned to normal levels. Conclusions: Gallbladder muscle from patients with cholesterol stones has increased membrane cholesterol/phospholipid mole ratio and decreased membrane fluidity resulting in impaired muscle contractility. These abnormalities are corrected by removing the excess cholesterol from the plasma membranes. GASTROENTEROLOGY 1999;116:678-685

Phenotypic Adaptation of Membrane Fluidity in the Tonoplast and Plasmalemma the C 3 Plant Hordeum vulgare cv. Alexis

Summary The influence of growth temperature and salinity stress on the fluidity of the tonoplast and plasmalemma in Hordeum vulgare cv. Alexis was studied. Membrane fluidity was monitored by measurements of fluorescence polarisation in membrane vesicles labeled with the fluorescent fatty acid analogue 1,6-diphenyl- 1,3,5-hexatrien (DPH) as a probe. It was found that, both in the tonoplast and plasmalemma, an increase in growth temperature lowered membrane fluidity, whereas lowering of growth temperature did the opposite. There is evidence that the rigidization of the membranes due to increase in growth temperature is mainly caused by membrane proteins. Accumulation of salt in the vacuoles of plants did not significantly shift the fluidity of the membranes, neither in the tonoplast nor in the plasmalemma. The results suggest that phenotypic adaptation of membrane fluidity also occurs in the tonoplast and plasmalemma of C3 plants, and not only in the tonoplast of CAM plants as previously reported.

Rat Erythrocyte Susceptibility to Lipid Peroxidation After Chronic Ethanol Intake

Erythrocytes, from 2- and 7-month-old rats chronically fed with a liquid diet containing ethanol, were analyzed for their susceptibility to lipid peroxidation estimated as thiobarbituric acid reactive substance (TBARS) products. In spite of a lower alcohol consumption, adult rats were the more affected by the ethanol treatment. Erythrocyte membranes prepared from alcoholic animals were more sensitive to lipid peroxidation than those prepared from control rats. In both age groups lipid analysis revealed similar changes: 1) an increased cholesterol/phospholipid molar ratio mainly derived from a higher content of cholesterol that accounts for the lower membrane fluidity and the higher tolerance to the disordering effect exerted by ethanol in vitro; 2) an increase of phospholipid unsaturated fatty acids, especially C20:4; 3) a modification of the phospholipid pattern, characterized in the ethanol group by an increase of PE and decrease of PE and decrease of PC levels; moreover, significant increases of the anionic phospholipids were detected in the adult group.

A membrane protein associated with the prolactin receptor studies with a photoactivatable human growth hormone derivative

Prolactin receptor from rat liver (PRL-R, 42 kDa) was cross-linked to a radiolabeled azidophenacyl derivative of human growth hormone ([ 125I]AP-hGH) to yield a 63 kDa adduct. In addition, a protein of Mr 50–52 K was detected as a 73 kDa complex. Microsomes incubated with either (a) increasing amounts of [ 125I]AP-hGH, or (b) a fixed amount of photoprobe and increasing concentrations of unlabeled hGH, showed that the 73/63 kDa band intensity ratio remains constant (0.71–0.77). Once transferred onto nitrocellulose membranes, only the 42 kDa protein is able to bind [ 125I]AP-hGH or [ 125I]hGH. Two anti-PRL-R monoclonal antibodies fail to cross-react with proteins of Mr 50–52 K. In membranes solubilized with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), a significantly lower amount of the 73 kDa complex is detected. Thus, the 50–52 kDa protein appears to be structurally unrelated to, but is presumably associated with the PRL-R. The 73 kDa complex is also detected under low membrane fluidity conditions (1 °C), indicating that PRL-R associates to this 50–52 kDa protein prior to hormone binding. Perfusion of rat liver with [ 125I]AP-hGH shows that this associated protein accompanies the receptor along its intracellular pathway.

Influence of equinatoxin II on coronary smooth muscle membrane fluidity.

Equinatoxin II forms pores in artificial as well as in natural phospholipid bylayers. As it also reduces the perfusion through the coronary arteries it seemed reasonable to investigate the interaction of this protein with the plasmalemma of the vascular smooth muscle cells more directly with the patch-clamp method and with EPR using the spin probe methyl ester of 5-doxylpalmitate. In the EPR spectra at least three regions in the membranes were identified with different membrane fluidity. Application of 0.1 microM or 1 microM equinatoxin II increases the portion with the lower membrane fluidity, and irreversibly increases the unspecific membrane conductance. This is compatible with the view that equinatoxin II forms pores in the membrane bilayer.

Erythrocyte Na+ -Li+ countertransport in essential hypertension

To examine whether Na(+)-Li+ countertransport (SLC) activity is linked to erythrocyte membrane lipid content. An observational case-control study. The maximal efflux rate of SLC, plasma cholesterol, triglycerides, phospholipids, low- and high-density lipoprotein cholesterol levels and the erythrocyte membrane cholesterol, phospholipids and fatty acids contents were determined both in fasting normolipaemic normotensive subjects and in hypertensive patients. The Li(+)-stimulated Na+ efflux was measured in Li(+)-preloaded erythrocytes. Membrane cholesterol and phospholipids levels were determined by the latroscan technique. Membrane fatty acids were identificated by gas chromatography. Several derived indices were also obtained. Erythrocyte membranes of hypertensive patients showed an increase in cholesterol: phospholipid ratio and a decrease in the total amount of polyunsaturated fatty acids, mainly at the expense of arachidonic acid and docosatetraenoic acid. SLC activity was higher in hypertensive patients and correlated positively with the plasma triglycerides level and negatively with the ratio of C20:4 to C20:3. Our data from untreated normolipaemic hypertensive patients show that a higher SLC activity was accompanied by parameters that indicate a lower membrane fluidity.

Modulation of Sperm Membrane Conformation by Pentoxifylline in Oligospermia: A Biophysical Investigation of Sperm Membranein Vitro

Low superoxide anion radical levels, low membrane fluidity and high superoxide dismutase activity are some of the defects existing in oligospermia. The phosphodiesterase inhibitor pentoxifylline has been used as a motility stimulant in the treatment of oligospermiain vitro.The mechanism of its action is unclear. Our results show significant inhibition of superoxide dismutase, increase in lipid peroxidation and membrane fluidity after pentoxifylline treatment. A biophysical modulation of the sperm membrane by an oxyradical mechanism in oligospermia is discussed.

Interactions of malondialdehyde and 4-hydroxynonenal with rat liver plasma membranes and their effect on binding of prostaglandin E2 by specific receptors.

We investigated effect of aldehydic products of lipid peroxidation, malondialdehyde (MDA) and 4-hydroxynonenal (HNE) on prostaglandin (PG) E2 receptors of liver plasma membranes. The modification of the membranes by MDA diminished PGE2 binding, decreasing receptor affinity for PGE2 and receptor density whereas HNE increased PGE2 binding, enhanced receptor density but did not changed receptor affinity. ESR study showed the decrease of the whole membrane fluidity after modification by MDA whereas HNE lowered membrane fluidity only in the internal zone of lipid bilayer and increased it in the surface area. The possible effects of membrane changes caused by MDA and HNE on PGE2 receptor parameters are discussed.

Effects of soybean-derived sterol and its glucoside mixtures added in dipalmitoylphosphatidylcholine liposomes on the blood circulation and hepatic cellular distribution in mice

The effects of a soybean-derived sterol mixture (SS) and their glucoside mixture (SG) in dipalmitoylphosphatidylcholine (DPPC) liposomes on blood circulation and hepatic distribution were investigated by measuring the leakage of calcein after intravenous administration to mice. Four kinds of liposomes were prepared: liposomes consisting only of DPPC (DPPC liposomes); and DPPC liposomes containing SS, cholesterol (Ch) or SG (molar ratio of DPPC/X = 7:2, X = SS, Ch, SG; SS, Ch and SG liposome), respectively. The area under the blood concentration-time curve (AUC) was greater in the order, SS liposomes > DPPC liposomes > SG liposomes, and the order is the same for lower membrane fluidity. Hepatic cellular distribution of SG liposomes 2 h after intravenous injection was significantly high compared with that of DPPC and SS liposomes. The results indicated that SS liposomes were stable in the blood circulation; however, SG liposomes were not stable and appeared to have an enhancing effect on hepatic uptake. This difference might indicate that hepatic accumulation is primarily governed by the glucose group of SG.

The relationship between membrane fluidity and permeabilities to water, solutes, ammonia, and protons.

Several barrier epithelia such as renal collecting duct, urinary bladder, and gastric mucosa maintain high osmotic pH and solute gradients between body compartments and the blood by means of apical membranes of exceptionally low permeabilities. Although the mechanisms underlying these low permeabilities have been only poorly defined, low fluidity of the apical membrane has been postulated. The solubility diffusion model predicts that lower membrane fluidity will reduce permeability by reducing the ability of permeant molecules to diffuse through the lipid bilayer. However, little data compare membrane fluidity with permeability properties, and it is unclear whether fluidity determines permeability to all, or only some substances. We therefore studied the permeabilities of a series of artificial large unilamellar vesicles (LUV) of eight different compositions, exhibiting a range of fluidities encountered in biological membranes. Cholesterol and sphingomyelin content and acyl chain saturation were varied to create a range of fluidities. LUV anisotropy was measured as steady state fluorescence polarization of the lipophilic probe DPH. LUV permeabilities were determined by monitoring concentration-dependent or pH-sensitive quenching of entrapped carboxyfluorescein on a stopped-flow fluorimeter. The relation between DPH anisotropy and permeability to water, urea, acetamide, and NH3 was well fit in each instance by single exponential functions (r > 0.96), with lower fluidity corresponding to lower permeability. By contrast, proton permeability correlated only weakly with fluidity. We conclude that membrane fluidity determines permeability to most nonionic substances and that transmembrane proton flux occurs in a manner distinct from flux of other substances.

Comparison of calcium,magnesiunn-ATPase activity and membrane fluidity in patients with essential hypertension and in normotensive controls

To measure calcium,magnesium-ATPase (Ca-ATPase) activity and membrane fluidity in patients with essential hypertension compared with normotensive subjects; to investigate the interrelationship between membrane fluidity and the activity of the Ca-ATPase; and to assess the importance of circulating lipids on the Ca-ATPase and membrane fluidity. Ca-ATPase and membrane fluidity were measured in erythrocyte membranes. Kinetic parameters [maximal activity (Vmax), apparent dissociation constant and allosteric number] of the Ca-ATPase activity were measured, in the presence of saturating calmodulin, in 38 normotensives and 57 essential hypertensives. Fluorescent polarization anisotropy, as an index of membrane fluidity, was measured, using the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium DPH (TMA-DPH) in 37 normotensives and 44 hypertensives. Of these 22 were paired for age, sex and race. There was no significant difference in the Vmax and allosteric number of the Ca-ATPase between the normotensives and hypertensives, but there was a trend for the hypertensives to have a reduced calcium affinity. In contrast, hypertensive subjects had significantly lower membrane fluidity. Sex and serum triglycerides level were important determinants of membrane fluidity in both groups. Comparisons between normotensives and hypertensives demonstrated decreased fluidity in the hypertensives independent of sex and serum triglycerides level, although the differences, especially with TMA-DPH, were more pronounced in the females. In both groups there were negative correlations between Vmax and both DPH and TMA-DPH anisotropy. The present study demonstrates that essential hypertension is associated with a generalized alteration in the erythrocyte membrane physical and chemical properties. However, despite the positive correlation between Vmax and membrane fluidity, the present study also demonstrates that essential hypertension is not associated with a major abnormality in the activity of the erythrocyte Ca-ATPase in isolated membranes.

Metal ions affect neuronal membrane fluidity of rat cerebral cortex

The effect of various metal ions on neuronal membrane fluidity was examined using 2-(14-carboxypropyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy, which has been used for the examination of membrane fluidity in hydrophobic areas by electron spin resonance spectrometry. Potassium, cobalt, calcium, magnesium, nickel, copper, ferric, and aluminium ions decreased the membrane fluidity while ferrous ions increased it at each high concentration. Sodium and zinc ions had no effect. Ethylenediaminetetraacetic acid decreased membrane fluidity at high concentrations. Nicardipine lowered membrane fluidity and flunarizine elevated it at each high concentration. There was no change in membrane fluidity by other calcium antagonists, nimodipine and nifedipine.

Abnormal Erythrocyte Rheology in Patients with Morbid Obesity

The objectives of this study were to investigate the rheological properties of the erythrocyte in patients with morbid obesity and to follow them up after a short-term weight loss. A fluorescent polarization method was used to assess erythrocyte membrane biorheology and to measure its fluidity. Eighteen subjects participated in the study: 8 healthy controls and 10 patients with morbid obesity. The erythrocyte membrane fluidity was obtained in the healthy subjects and in the patients with morbid obesity prior to and after a ten-day zero-calorie diet. Fluidity was determined by steady-state fluorescence polarization after incorporation of the lipophilic probe 1,6-diphenyl-1,3,5 hexatriene (DPH). With this method, the anisotropy parameter at 37 degrees C, which is inversely related to membrane fluidity, was obtained. The patients with morbid obesity revealed an abnormal erythrocyte rheology. The exhibited an abnormally low erythrocyte membrane fluidity as compared with normal subjects. The anisotropy parameter at 37 degrees C was 1.417 +/- 0.093 in these obese patients compared with 1.279 +/- 0.043 in normal-weight controls (p < 0.01). Upon a short-term significant weight loss from a body mass index (BMI) (weight/height2) of 39 +/- 5 to 36 +/- 5 kg/m2 (p < 0.05), the anisotropy parameter did not change (1.401 +/- 0.190). Thus, fluidity measurements permit recognition of an abnormal erythrocyte rheology in patients with morbid obesity. This abnormality may partially explain the excess cardiovascular and thromboembolic morbidity in morbid obesity.

Lowered membrane fluidity of younger erythrocytes in diabetes

In vivo age-related changes in membrane fluidity of erythrocytes were investigated by a spin label method after fractionation of the cells by discontinuous density gradient centrifugation. Membrane fluidity was lower in older than in younger erythrocytes in both the normal and diabetic subjects. Cells from diabetic subjects showed a significantly lower level of membrane fluidity for all three age groups (younger, middle and older) than the corresponding cells from normal subjects. The magnitude of progression in the decrease in membrane fluidity in erythrocytes did not differ significantly between both groups of subjects. Both erythrocyte ATP and acetylcholinesterase activity declined, while glycosylated hemoglobin (HbA 1c) increased with cell age in both groups of subjects. The HbA 1c level in each corresponding fraction was higher in diabetic subjects than normal subjects, but was not correlated with membrane fluidity in either group. Neither the ATP level nor acetylcholinesterase activity in each corresponding fraction differed between groups. Membrane fluidity was significantly correlated with acetylcholinesterase activity in both normal and diabetic subjects. Our results indicate that decreased erythrocyte membrane fluidity in diabetic patients does not form gradually during their life span but develops soon after the cells enter the circulation or during their maturation in the bone marrow.

Effect of ingestion of thermally oxidized frying oil on desaturase activities and fluidity in rat-liver microsomes

Fresh and thermally oxidized olive and sunflower oils were fed to rats at a practical level of concentration. Rats were fed a diet ad libitum for 10 months that contained 12% (wt/wt) of a test oil. Fatty acid composition of liver microsomes; physical state of the membrane lipids; and activities of the Δ 9, Δ 6, and Δ 5 desaturases were determined. The results demonstrate that dietary heated oils produce alterations in the desaturase activities of rat liver microsomes with concomitant changes in fatty acid composition of these membranes. Dietary heated oils accelerate the conversion of palmitic to palmitoleic acid by activating the Δ 9 desaturase activity and slow down the synthesis of arachidonic from linoleic acid by inhibiting the Δ 6 and Δ 5 desaturase activities in the rat liver microsomes. Fluorescence polarization studies, using diphenylhexatriene as a probe, showed lower membrane fluidity in olive oil groups than in sunflower oil groups. Moreover, there were significant differences between physical states of the membrane lipids from each group of the heated and non-heated oils. We concluded that thermally oxidized oils appear to produce alterations at the molecular level in the microsomes of rats, which are dependent on the composition of dietary lipids.

Platelet release products modulate some aspects of polymorphonuclear leukocyte activation

The aim of this research was to evaluate in vitro interactions between platelets and polymorphonuclear leukocytes. The effects of supernatant from thrombin-activated platelets and two platelet release products (adenosine triphosphate and beta-thromboglobulin) were tested on the following features of polymorphonuclear leukocytes activation: opsonized zymosan and phorbol myristate acetate stimulated chemiluminescence, release of membrane bound calcium, NADPH-oxidase activity, and membrane fluidity (fluorescent polarization). The results showed that the addition of platelet supernatant to polymorphonuclear leukocytes induces a significant activation of cells. On the other hand, after three hours of preincubation of polymorphonuclear leukocytes with platelet supernatant, a decreased response of polymorphonuclear leukocytes to stimulation with phorbol myristate acetate, a significant decrease in NADPH-oxidase activity, and a lowered membrane fluidity were observed. Adenosine triphosphate modulated only opsonized zymosan stimulated chemiluminescence, with and without preincubation with polymorphonuclear leukocytes. Beta-thromboglobulin caused a decrease of the chemiluminescent response of polymorphonuclear leukocytes, using both agonists, with and without preincubation with polymorphonuclear leukocytes. Moreover beta-thromboglobulin only caused a decrease of the polymorphonuclear leukocytes membrane fluidity without preincubation with the cells. These results support the thesis that platelets have a "time-related" modulating activity on polymorphonuclear leukocytes.

Relationship between vasopressin-sensitive water transport and plasma membrane fluidity in kidney collecting tubule

The role of plasma membrane fluidity in the regulation of kidney tubule water permeability has been uncertain. We have used new methods to image the fluorescence anisotropy of fluidity-sensitive fluorophores (Fushimi, Dix, and Verkman. Biophys. J. 57: 241-254, 1990) to quantitate membrane fluidity in cells of the vasopressin-sensitive cortical collecting tubule (CCT) and water-impermeable cortical thick ascending limb (CTAL). Isolated tubule segments from rabbit kidney were perfused in vitro, and apical or basolateral plasma membranes were stained with trimethylammonium diphenylhexatriene (TMA-DPH). TMA-DPH anisotropy (r) was imaged quantitatively by an epifluorescence microscope equipped with rotatable polarizers; TMA-DPH nanosecond lifetime (tau) was measured by flash-lamp excitation and gated photomultiplier detection. In CCT, apical membrane r (0.254 +/- 0.003) was similar to basolateral r (0.252 +/- 0.005). Serosal vasopressin at a dose that increased water permeability greater than 10-fold (250 microU/ml) did not affect apical membrane r (delta r = 0.002 +/- 0.003; 7 tubules). A 0.002 change in r was less than that produced by a 2 degrees C temperature variation. In CTAL, apical membrane r was 0.249 +/- 0.002, similar to r from basolateral membrane of proximal tubule (0.24), but much less than that of proximal tubule apical membrane (0.29). These results establish methodology to quantitate fluidity in intact kidney tubule segments and provide the first measurements of plasma membrane fluidity in CTAL and CCT. Our results suggest that regulation of bulk membrane fluidity in CCT apical membrane is not a component of the hydrosmotic action of vasopressin and that low apical membrane fluidity is not responsible for the low water and NH3 permeabilities in CTAL.

Regulation of chloride transport in parotid secretory granules by membrane fluidity

Zymogen granule membranes contain Cl- conductance and Cl/anion exchange activities that become important for primary fluid production after fusion with the apical plasma membrane of the acinar cell. We have used steady-state fluorescence anisotropy of diphenylhexatriene derivatives and measurements of Cl- transport in isolated secretory granules to determine the contribution of membrane fluidity to the regulation of transport across the granule membrane. Secretory granules from several unstimulated glands (rat pancreas and parotid, rabbit gastric glands) were shown to have low membrane fluidity compared to plasma membranes. In addition, Cl- transport activity in different granule preparations showed a strong correlation to the membrane fluidity when measured with 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene p-toluenesulfonate (TMA-DPH), but not with 3-[p-(6-phenyl)-1,3,5-hexatrienyl)-phenyl]propionic acid (PA-DPH). These data suggest that TMA-DPH preferentially partitions into a specific lipid environment associated with, or which exerts an influence on, the Cl- transport proteins and that increases in the fluidity of this environment are associated with higher transport rates. Data from other types of plasma membranes indicate that TMA-DPH partitions much more than PA-DPH into the cytoplasmic leaflet, suggesting that this part of the granule membrane is involved in the observed fluidity changes. Furthermore, increasing the bulk membrane fluidity with the local anesthetics benzyl alcohol and n-alkanols increased the Cl- transport rates up to 10-fold. This increase was apparently through specific transporters as anion selectivity was maintained in spite of the higher absolute rates.(ABSTRACT TRUNCATED AT 250 WORDS)

リポソーム封入シスプラチンによる脳腫ようターゲッテング療法 １ 構造変換リポソームと脳腫よう指向性

The chemotherapeutic anticancer agent cisplatin (cis-diamminedichloroplatinum, CDDP) has several disadvantages, such as its extreme nephrotoxity and rapid binding to plasma proteins, and also poor penetration in the central nervous system, Liposomes therefore seemed to be suitable carriers to overcome these problems. Liposomes were investigated as a carrier for the delivery of therapeutic agents to target brain tumors. Four kinds of liposomes were prepared : neutrial liposome (phosphatidylcholine and cholesterol), positively charged liposome (added stearyl amine), negatively charged liposome (added phosphatidic acid) and neutral liposome with low membrane fluidity (dipalmitoylphosphatidylcholine and cholesterol). As for the uptake of radioactivity in the brain tumor, spleen, liver, kidney and brain 30 minutes after the injection of liposomes labeled with 14C into the 9L cells implanted brain tumor rats, the spleen had the highest uptake of radioactivity. The uptake was also greater in the brain tumor and lower in the kidney as compared to using cisplatin alone. The brain tumor uptake were in order of neutral liposome with low membrane fluidity, neutral liposome, negatively charged liposme and positively charged liposome. The cytotoxity of cisplatin against 9L-glioma cells was not decrease by encapsulation of liposomes. These results indicate that liposomesencapsulated cisplatin could be utilized for targeting the chemotherapy of brain tumors, however in order to increase the targetability of liposome to brain tumors, we have developed the coating of liposomes with a cell specific polysaccharide.

Deficiencies of polyunsaturated fatty acids and replacement by nonessential fatty acids in plasma lipids in multiple sclerosis.

Fatty acid compositions of plasma phospholipids, cholesteryl esters, triacylglycerols, and nonesterified fatty acids of 14 clinically proven and graded cases of multiple sclerosis were determined by capillary gas chromatography and compared with the values obtained for 100 normal, healthy subjects. In phospholipids, linoleic acid (18:2 omega 6; 18 carbon atoms, 2 double bonds, 6 carbon atoms beyond last double bond) was normal and 18:3 omega 6 was increased, but all subsequent omega 6 acids were subnormal (P less than 0.001), indicating impairment of chain elongation. All omega 3 acids were subnormal. The paucity of polyunsaturated fatty acids was compensated mass-wise by an increase in saturated acids. Disproportionate increases in short-chain, saturated, and monounsaturated acids, decreases in long-chain homologs, and increases of branched and odd-chain acids were observed. Loss of polyunsaturated fatty acids and replacement by nonessential acids lowered mean chain length and raised mean melting point significantly, suggesting that lowered membrane fluidity was only partially compensated by endogenous synthesis of lower-melting, nonessential acids. This phenomenon was not observed in cholesteryl esters or triacylglycerols. Nonesterified fatty acids showed significant changes in pattern of possible autacoid precursors. The abnormal profile of fatty acids in multiple sclerosis has features in common with profiles of other syndromes involving viral infections.