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PubMedDate not supplied

[Heat induced structural transformations in Escherichia coli membranes in the presence of Ca2+].

Using an uncharged hydrophobic fluorescent probe 4-dimethylaminochalkon (DMC) the thermotropic behaviour of cytoplasmic E. coli membranes in the presence of Ca2+ cations was investigated. DMC appeared to be very sensitive in detection of temperature induced phase transitions in E. coli membrane preparations. It was found unexpectedly that Ca2+ does not increased the phase transition temperature of membrane preparations, compared to the values calculated for the membranes in tris-HC1-buffer. The obtained results are briefly discussed.

Calcium↗

PubMed2002

Acid-induced changes in thermal stability and fusion activity of influenza hemagglutinin.

The conformational and thermal stability of full-length hemagglutinin (HA) of influenza virus (strain X31) has been investigated using a combination of differential scanning calorimetry (DSC), analytical ultracentrifugation, fluorescence, and circular dichroism (CD) spectroscopy as a function of pH. HA sediments as a rosette comprised of 5-6 trimers (31-35 S) over the pH range of 7.4-5.4. The DSC profile of HA in the native state at pH 7.4 is characterized by a single cooperative endotherm with a transition temperature (Tm) of 66 degrees C and unfolding enthalpy (DeltaH(cal)) of 800 kcal x (mol of trimer)(-1). Upon acidification to pH 5.4, there is a significant decrease in the transition temperature (from 66 to 45 degrees C), unfolding enthalpy [from 800 to 260 kcal x (mol of trimer)(-1)], and DeltaH(cal)/DeltaH(vH) ratio (from 3.0 to approximately 1.3). Whereas the far- and near-UV ellipticities are maintained over this pH range, there is an acid-induced increase in surface hydrophobicity and decrease in intrinsic tryptophanyl fluorescence. The major contribution to the DSC endotherm arises from unfolding HA1 domains. The relationship between acid-induced changes in thermal stability and the fusion activity of HA has been examined by evaluating the kinetics and extent of fusion of influenza virus with erythrocytes over the temperature and pH range of the DSC measurements. Surprisingly, X31 influenza virus retains its fusion activity at acidic pH and temperatures significantly below the unfolding transition of HA. This finding is consistent with the notion that the fusion activity of influenza virus may involve structural changes of only a small fraction of HA molecules.

Acids↗

PubMed2006

Structural hierarchy in melt-processed poly(3-hexyl thiophene)-montmorillonite clay nanocomposites: novel physical, mechanical, optical, and conductivity properties.

Poly(3-hexyl thiophene) (P3HT) organically modified montmorillonite (om-MMT) polymer nanocomposites (PNCs) are prepared in the melt-cooled state. Hierarchical structures up to third order, namely, side chain mesomorph formation followed by the interchain lamellar structure of P3HT and finally its intercalation within the clay tactoids are observed. The structures are supported by transmission electron microscopy (TEM) and wide-angle X-ray scattering (WAXS) experiments. The TGA curves show two-stage degradation corresponding to those of the side chain and main chain of P3HT, and both temperatures decrease with an increase in clay concentration in the PNCs. The melting points of PNCs have increased by 2-3 degrees C higher than that of P3HT. The glass-transition temperature (Tg) and beta-transition temperature (Tbeta), measured by DMA, increase with an increase in clay concentration. The storage modulus (G) of PNCs has also increased more dramatically than that of P3HT. The UV-vis spectra of the PNCs show a blue shift in the pi-pi* absorption peak of the conjugated chain, but the photoluminescence spectra showed a red shift with an increase in the clay concentration. The quantum yield of the photoluminescence process also increases in the melt-cooled PNCs, and this is in sharp contrast to that of solvent cast PNCs where photoluminescence quenching was observed. Fibrillar network structure of the solvent cast PNCs promotes energy transfer of the charge carriers, but its absence in the melt-cooled films inhibits such energy transfer, increasing the quantum yield. The room-temperature dc conductivity of the PNCs decreased by an order compared to that of P3HT in both the doped and undoped states. The I-V characteristic curve shows semiconducting behavior, and it slowly transforms into insulator with increasing clay concentration.

Journal Article↗

PubMed2003

Characterization of temperature dependent mechanical behavior of cartilage.

BACKGROUND AND OBJECTIVES: Few quantitative studies have investigated the temperature dependent viscoelastic properties of cartilage tissue. Cartilage softens and can be reshaped when heated using laser, RF, or contact heating sources. The objectives of this study were to: (1) measure temperature dependent flexural storage moduli and mechanical relaxation in cartilage, (2) determine the impact of tissue water content and orientation on these mechanical properties, and (3) use these measurements to estimate the activation energy associated with the mechanical relaxation process. STUDY DESIGN/MATERIALS AND METHODS: Porcine nasal septal cartilage specimens (30 x 10 x 2 mm) were deformed using a single cantilever arrangement in a dynamic thermomechanical analyzer. Stress relaxation measurements were made at discrete temperatures ranging from 25 to 70 degrees C in response to cyclic deformation (within the linear viscoelastic region). The time and temperature dependent behavior of cartilage was measured using frequency multiplexing techniques (10-64 Hz), and these results were used to estimate the activation energy for the phase change using the Williams-Landel-Ferry (WLF) equation and the Arrhenius kinetic equation. In addition, the effect of tissue orientation was examined with specimens oriented in both transverse and longitudinal directions at room temperature. RESULTS: The storage moduli of porcine cartilage decreased with increasing temperature, and a critical change in mechanical properties was observed between 58 and 60 degrees C with a reduction in the storage modulus by 85-90%. The shift of the stress relaxation behavior from viscoelastic solid to viscoelastic liquid was observed between 50 and 57 degrees C and likely corresponds to the transition temperature region in which structural changes in the tissue occur. The storage moduli for transverse and longitudinally oriented specimens were 19-22 and 14-16 MPa, respectively at ambient temperature. Reducing the water content (<10% mass loss) by allowing it to dry under ambient conditions resulted in reduction in the storage modulus by 31-36%. The activation energy associated with the mechanical relaxation of cartilage was 147 kJ/mole at 60 degrees C. This value was calculated by measuring stress-strain relationship under conditions where linear viscoelastic behavior was observed (0.09-0.15% of strain) within the transition temperature region (58-60 degrees C). CONCLUSIONS: The anisotropic mechanical behavior of cartilage was quantitatively analyzed in the transversely and longitudinally oriented specimens. Viscoelastic behavior appeared to be strongly dependent on the water content. Using empirically determined estimates of the transition zone temperature range accompanying stress relaxation, the activation energy for stress relaxation was calculated using time and temperature superposition theory and WLF equation. Further investigation of the molecular changes, which occur during laser irradiation, may assist in understanding the thermal and mechanical behavior of cartilage and how the reshaping process might to be optimized.

Animals↗

PubMedDate not supplied

Modification of dry 1,2-dipalmitoylphosphatidylcholine phase behavior with synthetic membrane-bound stabilizing carbohydrates.

Carbohydrates, particularly disaccharides, have been shown to accumulate in organisms as protective solutes during periods of stress such as freezing and desiccation. Cholesterol and lipid derivatives containing the protective carbohydrates galactose or maltose, O-[11-(1-beta-D-galactosyloxy)-3,6,9-trioxaundecanyl]ol (TEC-GAL), O-[11-(1-beta-D-maltosyloxy)-3,6,9-trioxaundecanyl]ol (TEC-MAL), and 14-(galactosyloxy)-N,N-dimethyl-O-(dipalmitoylphosphatidyl)- 6,9,12-trioxa-3- azoniatetradecanol (DP-GAL), have been synthesized to investigate the interaction of a protective carbohydrate moiety tethered to the 1,2-dipalmitoylphosphatidylcholine (DPPC) bilayer surface. Toward this goal, we have investigated the calorimetric and infrared spectroscopic behavior of mixtures of DPPC codried with these glycolipids. The synthetic glycolipids are shown to decrease significantly the main transition temperature (max Cp) of dry DPPC with a concomitant reduction in the cooperativity of the transition, as evidenced by a decrease in the enthalpy with increasing glycolipid. The decrease in transition temperature is shown to be related to chain melting monitored by the CH2 symmetric stretch frequency through the transition using FTIR. We also present evidence that the glycolipids interact with the interfacial region of DPPC, as shown by the decrease in the phosphate symmetric stretch intensity with increasing concentration of glycolipid. These observed effects are similar to the action of bulk protective sugars with DPPC; however, the concentration of glycolipid and the associated carbohydrate concentration needed to effect the observed changes are reduced compared to the quantity of bulk carbohydrate previously shown to give similar results with DPPC.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1987

Effect of myelin basic protein on the thermotropic behavior of aqueous dispersions of neutral and anionic glycosphingolipids and their mixtures with dipalmitoylphosphatidylcholine.

The thermotropic behavior of the natural glycosphingolipids galactosylceramide, asialo-Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-4Glc beta 1-Cer (GM1), sulfatide, GM1, NeuAc alpha 2-3Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-4Glc beta 1-1Cer (GD1a), and NeuAc alpha 2-3Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc8-2 alpha NeuAc)beta 1-4Glc beta 1-1 Cer (GT1b), and their mixtures with dipalmitoylphosphatidylcholine (DPPC) in the presence of myelin basic protein (MBP) was studied by high sensitivity differential scanning calorimetry. The transition temperature of DPPC, galactosylceramide, and asialo-GM1 is affected little by MBP while their transition enthalpy is decreased in proportion to the amount of protein in the mixture. The thermotropic behavior of anionic glycosphingolipids is considerably perturbed by MBP. The transition temperature of gangliosides increases in the presence of MBP, whereas that of sulfatide decreases. The enthalpy of the transition of anionic glycosphingolipids increases markedly in the presence of MBP. The excess heat capacity function of these systems can be resolved into two independent phase transitions. Phase separation of enriched lipid/protein domains occurs in a magnitude that depends on the amount of MBP; the rest of the lipid phase exhibits some altered thermodynamic properties. In mixtures of glycosphingolipids with DPPC, phase separation is also present but no phase transition with the characteristic of pure DPPC is found. MBP is changing the properties of the lipid mixture as a whole and does not interact exclusively with the glycosphingolipids. The proportion of MBP required to produce the maximal changes is greater the greater the complexity of the glycosphingolipids polar head group. Relatively small variations of the amount of MBP induce large shifts in the proportion of the different phases present.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1977

Effect of double-bonds on bimolecular films in membrane models.

The effect of unsaturation (especially by cis-bonds) is studied on bimolecular films of saturated and unsaturated alkylammonium ions and alkanols between silicate surfaces as model systems for lipid layers in membranes. Three types of structures are observed: all-trans-blocks, kink-blocks and gauche-blocks. The knowledge of the sequence of these phases and their thermal transitions provides detailed deductions about the role of double-bonds. cis-Unsaturated chains are taken up in bimolecular films as isomers with cis-trans-gauche conformation. This conformation makes the shape of the chain similar to that of kinked chains (chains with gauche-trans-gauche (--) conformation) and enables the incorporation into the film without greater sterical hindrance. The experimental results are in good agreement with X-ray measurements on biological membranes by Engelman (Engelman, D.M., J. Mol. Biol. 47, 115--117 (1970) and 58, 153--165 (1971)). Increasing the concentration of cis-chains decreases the transition temperature of the kink-blocks into gauche-blocks. The variation of the transition temperature with concentration of cis-unsaturated chains in the model system is similar to that observed for Escherichia coli membranes. It is suggested that phase changes in biomembranes are of the same nature: transition of kink-block analogues as ordered phases into gauche-block assemblies as less ordered phases.

Calcium↗

PubMed1980

Thermal stability of poly(A) and poly(U) complexes in H2O and D2O: isotopic effects on critical temperatures and transition widths.

This is a study of the effect of total and partial deuteration of solvent on critical temperatures and profiles of all four reactions occurring in poly(A) x n poly(U) (n = 1 or 2) aqueous systems. The study was done at observational times not longer than hydrogen exchange times at base pairs in helically ordered structures, and it was extended to a wide range of salt concentrations at neutral pH. The dependence of stability of polymer helical order on hydrogen mass does not appear to be merely attributable to the stronger intrahelical deuterium bonding. Substituting Deuterium for Hydrogen implies a probably predominant modulation of the entrophy term of polymer-solvent interactions. Effects of deuteration on the width of the 2(poly(A) x poly (U)) leads to poly(A) x 2poly(U)+poly(A) interconversion reaction were also observed. They bear on the role of polymer-solvent interaction on pattern recognition leading to formation of ordered structures. They also bear on the role of the same interaction on the "breathing" of ordered structures of this type.

Deuterium↗

PubMed2002

Characterization of the thermal properties of microcrystalline cellulose by modulated temperature differential scanning calorimetry.

The purpose of this study was to characterize the thermal properties of microcrystalline cellulose (MCC) and to investigate the influence of water on these properties. Differential scanning calorimetry (DSC), modulated temperature differential scanning calorimetry (MTDSC), thermomechanical analysis (TMA), and scanning electron microscopy (SEM) were used to characterize MCC. Three reproducible step transitions were detected in the dry material at 132, 159, and 184 degrees C; for these transitions the magnitude of the heat capacity change varied by a factor of two. Exposure of MCC to water lowers the transition temperature in a manner comparable to a glass transition. The effect of water was different for samples equilibrated to different atmospheric humidities versus water added by granulation. A change in the physical properties of MCC after granulation with high amounts of water was observed. In conclusion, it appears that MCC has glass transitions, which come in reproducible triplets, and these transitions are affected by the presence of water. Also, for the materials studied, the transition temperatures are not affected by particle size and pulp source.

Calorimetry, Differential Scanning↗

PubMed1991

The effect of hydration stress solutes on the phase behavior of hydrated dipalmitoylphosphatidylcholine.

We have investigated the interaction of solutes found to accumulate in biological systems during chilling, dehydration, and salt stress with fully hydrated multilamellar and unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). We have focused on a series of mono-, di-, and tri-substituted amines (glycine, 4-hydroxyproline, proline, and betaine) and contrasted the action of these solutes to trehalose, a protective disaccharide. Differential scanning calorimetry studies show that when DPPC is scanned in the presence of increasing concentrations of these solutes (up to 3 M), there is a moderate increase in the pre-transition temperature (1-6 degrees C) with a smaller increase (1-2 degrees C) in the main transition temperature of hydrated multilamellar vesicles of DPPC. Other calorimetric parameters (delta H, delta T1/2, Cpmax) determined for the pre-transition and main transition were similar independent of the solute. In each case, the main phase transition was broadened with increasing solute while the transition enthalpy was not significantly affected.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2006

Drugs acting as plasticizers in polymeric systems: a quantitative treatment.

The objective of the present study was to investigate and quantify the effects of ibuprofen, chlorpheniramine maleate and metoprolol tartrate on the thermal, mechanical and diffusional properties of polyacrylate-based films. Thin drug-containing films were prepared from organic Eudragit RS solutions and physicochemically characterized with respect to their glass transition temperature, mechanical properties and drug release kinetics in phosphate buffer pH 7.4. The apparent diffusion coefficient of the drug within the polymeric systems was determined by fitting an adequate solution of Fick's second law of diffusion to the experimentally determined release profiles. Importantly, the glass transition temperature of the films significantly decreased with increasing initial drug content, whereas the film flexibility and drug release rate increased. This clearly indicates that the three drugs act as efficient plasticizers for Eudragit RS. Interestingly, the mathematical analysis revealed that drug release was primarily controlled by diffusion. An increase in the initial drug content resulted in increased drug diffusivities and, thus, accelerated (absolute and relative) drug release rates. Importantly, quantitative relationships could be established between the drug diffusivity and the initial drug content. Based on this knowledge, the effects of the films' composition and thickness on the resulting drug release kinetics (also from coated solid dosage forms) can be predicted in a quantitative way.

Chemistry, Pharmaceutical↗

PubMed1993

Contribution of loops and nicks to the formation of DNA dumbbells: melting behavior and ligand binding.

We have evaluated the thermodynamic contribution of thymine loops and nicks to the overall stability of double-helical DNA by investigating (1) the melting behavior of two unligated DNA dumbbells and their corresponding core duplexes and (2) the association of netropsin to the central core of four A.T base pairs of these molecules. Temperature-dependent UV absorption and differential scanning calorimetry techniques have been used to characterize the helix-coil transitions of all four deoxyoligonucleotide duplexes. In 10 mM NaP(i) buffer at pH 7.0, all transitions were monophasic. The dumbbells melt with transition temperatures, Tm, independent of strand concentration, while each duplex melts with transition temperature dependence on strand concentration, characteristic of mono- and bimolecular processes, respectively. The Tm's for the dumbbells correspond to those of single hairpins containing only four base pairs in the stem. We obtain dTm/d log [Na+] values of 10.9-12.5 degrees C for these molecules, which correspond to similar counterion releases and suggest helical structures with similar charge densities and helical strandedness. Standard thermodynamics profiles at 5 degrees C reveal that the favorable free energy of forming these ordered structures results from the partial compensation of favorable enthalpies with unfavorable entropies. The stabilization of the dumbbells relative to the core duplexes is enthalpic, due to extra stacking of the nearest loop thymines on the G.C base pairs at both ends of the stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1984

Interactions of phospholipid monolayers with carbohydrates.

Surface pressure studies of phospholipid monomolecular films of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) formed at an air/water interface have been made and the effects on the films studied when various carbohydrates are present in the subphase. The results obtained show that at a given temperature, the area per molecule of DPPC increases with increasing concentration of the carbohydrate in the subphase. The carbohydrate which has the greatest expanding effect on the phospholipid monolayer is glycerol, followed in turn by trehalose, sucrose, glucose, raffinose, and inositol. The mechanism of monolayer expansion by glycerol is different from that observed in other carbohydrates, as the following experiments demonstrate. Below the phase transition temperature of DPPC, the area per molecule of DPPC at a pressure of 12.5 dyn/cm is the same with and without glycerol in the subphase. However, when the monolayer is heated to a temperature above the phase transition temperature for DPPC, the area/molecule on glycerol is considerably greater than the area/molecule on water at the same surface pressure. Cooling the monolayer back to the lower temperature produces an area/molecule of DPPC which is identical on both water and glycerol subphases. Glycerol therefore has no effect on the low-temperature (condensed) monolayers but causes expansion of the high-temperature (expanded) monolayers. By contrast with glycerol, both trehalose and sucrose interact with the DPPC monolayer producing an increased area/molecule over that observed on water, both with low-temperature (condensed) monolayers and with the high-temperature (expanded) monolayers. The efficiency of these carbohydrates at expanding the monolayer films (with the exception of glycerol) shows a strong correlation with their ability to stabilize membrane structure and function at low water contents.

Carbohydrates↗

PubMed1989

Sensitivity of Altitudinal Ecotypes of the Wild Tomato Lycopersicon hirsutum to Chilling Injury.

The transition temperature of the leaf polar lipids and the critical temperature for chill-induced inhibition of photosynthesis was determined for three altitudinal ecotypes of the wild tomato Lycopersicon hirsutum. Photosynthesis was measured as CO(2)-dependent O(2) evolution at 25 degrees C after leaf slices were exposed to chilling temperatures for 2 hours at a moderate photon flux density of 450 micromoles per square meter per second. The transition temperature of the leaf polar lipids was detected from the change in the temperature coefficient of the fluorescence intensity of trans-parinaric acid. Chill-induced photoinhibition was evident in the three tomato ecotypes when they were chilled below a critical temperature of 10 degrees , 11 degrees , and 13 degrees C, respectively, for the high (LA1777), mid (LA1625), and low (LA1361) altitudinal ecotypes. The temperature differential, below the critical temperature, required to produce a 50% inhibition was also similar for the three ecotypes. A transition was detected in the leaf polar lipids of these plants at a temperature similar to that of the critical temperature for photoinhibition. The results show that the three tomato ecotypes are similar with respect to their critical temperature for chilling-induced photoinhibition and the rate of their response to the chilling stress. They are, thus, similarly sensitive to chilling.

Journal Article↗

PubMed2000

Polymer principles of protein calorimetric two-state cooperativity.

The experimental calorimetric two-state criterion requires the van't Hoff enthalpy DeltaH(vH) around the folding/unfolding transition midpoint to be equal or very close to the calorimetric enthalpy DeltaH(cal) of the entire transition. We use an analytical model with experimental parameters from chymotrypsin inhibitor 2 to elucidate the relationship among several different van't Hoff enthalpies used in calorimetric analyses. Under reasonable assumptions, the implications of these DeltaH(vH)'s being approximately equal to DeltaH(cal) are equivalent: Enthalpic variations among denatured conformations in real proteins are much narrower than some previous lattice-model estimates, suggesting that the energy landscape theory "folding to glass transition temperature ratio" T(f) /T(g) may exceed 6.0 for real calorimetrically two-state proteins. Several popular three-dimensional lattice protein models, with different numbers of residue types in their alphabets, are found to fall short of the high experimental standard for being calorimetrically two-state. Some models postulate a multiple-conformation native state with substantial pre-denaturational energetic fluctuations well below the unfolding transition temperature, or predict a significant post-denaturational continuous conformational expansion of the denatured ensemble at temperatures well above the transition point, or both. These scenarios either disagree with experiments on protein size and dynamics, or are inconsistent with conventional interpretation of calorimetric data. However, when empirical linear baseline subtractions are employed, the resulting DeltaH(vH)/DeltaH(cal)'s for some models can be increased to values closer to unity, and baseline subtractions are found to correspond roughly to an operational definition of native-state conformational diversity. These results necessitate a re-assessment of theoretical models and experimental interpretations.

Calorimetry↗

PubMed1983

Mechanical properties of hydrophilic copolymers of 2-hydroxyethyl methacrylate with ethyl acrylate, n-butyl acrylate, and dodecyl methacrylate.

Copolymers were prepared of 2-hydroxyethyl methacrylate, which is strongly hydrophilic, with hydrophobic comonomers having a low glass transition temperature, i.e., ethyl acrylate, n-butyl acrylate, and dodecyl methacrylate. The glass transition temperature, T alpha (1 Hz), of polymers in the dry state (xerogels) was determined by means of dynamic mechanical measurements. The dependence of T alpha on composition in all the three series of copolymers was described in terms of a one-parameter equation. The equilibrium swelling of copolymers in water decreases more steeply than the weight fraction of 2-hydroxyethyl methacrylate. When swollen in water to equilibrium, all copolymers with ethyl acrylate or n-butyl acrylate are in the rubberlike state; their tensile modulus E assumes values in the range 0.17-0.50 MPa. While poly(2-hydroxyethyl methacrylate) has the modulus E = 0.39 MPa, the tensile strength sigma u = 0.32 MPa, and the strain-at-break epsilon u = 1.81, for the weight fraction of the comonomer in the range 0.36 less than or equal to omega 2 less than or equal to 0.56 it is possible to achieve sigma u and epsilon u lying in the respective ranges 0.7-0.9 MPa and 5-7. Copolymers with the dodecyl methacrylate content omega 2 less than 0.2 or omega 2 greater than 0.8 are rubberlike, and at 0.30 less than or equal to omega 2 less than or equal to 0.62 they become leathery; the latter have the modulus E and strength sigma u within the ranges 12-32 and 3-4 MPa, respectively. The stress-strain curves of these copolymers evidence yielding and orientation hardening which have been tentatively explained by the nonhomogeneous composition and structure of the copolymers.

Acrylates↗

PubMed1992

Novel acrylic resins for dental applications.

A heat-cured resin based on a copolymer of bis-phenol-A glycidyl methacrylate (bis-GMA) and tetrahydrofurfuryl methacrylate (THFM) was investigated. Workable pastes were made by adding 90/10 w/w bis-GMA/THFM copolymer powder to a 70/30 w/w monomer of the same composition. The organic filler content was 60-64% w/w. Young's modulus, flexural strength, impact strength, hardness, water absorption and desorption, linear thermal expansion, polymerization shrinkage and glass transition temperature were determined. The materials studied showed high elastic modulus, hardness and glass transition temperature. A relatively low linear thermal expansion was obtained but poor impact strength and low flexural strength, indicating brittleness. Acceptable values were obtained for water absorption.

Acrylic Resins↗

PubMed1991

Action of insulin in rat adipocytes and membrane properties.

Several small peptides inhibit insulin-promoted glucose uptake in rat adipocytes. At 10 microM peptide concentration, the extent of their inhibition of the insulin effect is related to the ability of these peptides to raise the bilayer- to hexagonal-phase transition temperature in model membranes. Hexane and DL-threo-dihydrosphingosine lower this phase transition temperature in model membranes, and they promote glucose uptake in adipocytes. There is thus an empirical relationship between the action of membrane additives on glucose uptake in adipocytes and their effect on the hexagonal-phase-forming tendency in model membranes. The most potent of the bilayer-stabilizing peptides tested in this work is carbobenzoxy-D-Phe-L-Phe-Gly. This peptide also inhibits insulin-stimulated protein synthesis in adipocytes. In contrast, DL-threo-dihydrosphingosine stimulates protein synthesis. The uptake of [125I]iodoinsulin by adipocytes is inhibited by carbobenzoxy-D-Phe-L-Phe-Gly. The mechanism of action of the bilayer-stabilizing peptides includes inhibition of insulin-dependent protein phosphorylation in adipocytes. The peptides are not specific inhibitors of a single function but are suggested to cause their effects by altering the physical properties of the membrane in a nonspecific manner. These results demonstrate that insulin-dependent functions of rat adipocytes can be modified by membrane additives in a manner predictable from the properties of these additives in model membranes.

Adipose Tissue↗