Biomedical subjects

G Cevc

Publications and source records attributed to G Cevc.

At least 37 records · Page 2Linked to original sources

PubMed1995

Transdermal immunization with large proteins by means of ultradeformable drug carriers.

By means of novel, ultradeformable and self-optimizing agent carriers called transfersomes, large molecules can be brought into the body through intact permeability barriers. This permits non-invasive immunization through normal skin and gives rise to a similar or even slightly higher antibody titer than subcutaneous injections of the same immunogen formulation. The former type of immunization also results in a higher IgA/IgG ratio in the blood than the repeated immunogen injections, as shown here for a soluble protein, human serum albumin, as well as for an integral membrane protein, gap junction protein, in mice.

Administration, Cutaneous↗

PubMed1995

Lateral electrical conductivity of mica-supported lipid bilayer membranes measured by scanning tunneling microscopy.

Lateral electric conductivity of mica-supported lipid monolayers and of the corresponding lipid bilayers has been studied by means of scanning tunneling microscopy (STM). The surface of freshly cleaved mica itself was found to be conductive when exposed to humid air. Lipid monolayers were transferred onto such a surface by means of the Langmuir-Blodgett technique, which makes the mica surface hydrophobic and suppresses the electric current along the surface in the experimentally accessible humidity (5-80%) and applied voltage (0-10 V) range. This is true for dipalmitoylphosphatidylethanolamine (DPPE) as well as dipalmitoylphosphatidylcholine (DPPC) monolayers. Repeated deposition of DPPC layers by means of the Langmuir-Blodgett LB technique does not lead to the formation of a stable surface-supported bilayer because of the high hydrophilicity of the phosphatidylcholine headgroups that causes DPPC/DPPC bilayers to peel off the supporting surface during the sample preparation. In contrast to this, a DPPE or a DPPC monolayer on top of a DPPE monolayer gives rise to a rather stable mica-supported bilayer that can be studied by STM. Electric currents between 10 and 100 fA, depending on the ambient humidity, flow along the DPPE bilayer surface, in the humidity range between 35 and 60%. The DPPC surface, which is more hydrophilic, is up to 100 times more conductive under comparable conditions. Anomalous high lateral conductivity thus depends on, and probably proceeds via, the surface-adsorbed water layers. The prominence of ambient humidity and surface hydrophilicity on the measured lateral currents suggests this. The combination of our STM data and previously published water adsorption isotherms as a function of the relative humidity indicate that one layer or less of adsorbed water suffices for mediating the measurable lateral currents. The fact that similar observations are also made for other hydrophilic substrates supports the conclusion that lateral conductivity via surface-adsorbed water is a rather general phenomenon.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

Temperature- and pH-controlled fusion between complex lipid membranes. Examples with the diacylphosphatidylcholine/fatty acid mixed liposomes.

The fusion capability of complex lipid bilayers and its pH as well as temperature sensitivity have been studied by optical and spectroscopic means. The aggregation and fusion efficiency of such lipid membranes can be optimized by controlling the phase characteristics of the individual membrane components. For a practically relevant illustration, the stoichiometric 1:2 (mol/mol) mixtures of phosphatidylcholines and fatty acids are used. Perhaps the most interesting liposomes of this kind, which are made of dipalmitoylphosphatidylcholine/elaidic acid (DPPC/ELA-COOH (1:2)), undergo a chain-melting phase transition between 42 degrees C and 48 degrees C, depending on the bulk pH value. The highest chain-melting phase transition temperatures are measured with the fully protonated fatty acids at pH < or = 5.5 and involve a change into the non-bilayer high-temperature state. Upon increasing pH, this transition reverts into an ordinary gel-to-fluid lamellar phase change and occurs at 42 degrees C, by and large. Simultaneously, the rate and the efficacy of fusion between the PC/FA and PC/FA- mixed vesicles decreases. The fusion efficacy of the PC/FA(-) mixed liposomes at pH > or = pK(FA) approximately 7.5 is practically negligible. This is largely due to the increased interbilayer repulsion and to the relatively high water-solubility of the deprotonated fatty acid molecules at high pH. While the pH-variability chiefly affects the efficacy of the intermembrane aggregation, the vesicle fusion itself is more sensitive to temperature variations. It is more likely that the temperature dependence of the intramembrane defect density is chiefly responsible for this. Optimal conditions for the fusion between DPPC/ELA-COOH (1:2) mixed vesicles are thus 3.5 < or = pH < or = 5.5 (6.3) (aggregation maximum) and T > or = 41.5 degrees C = Tm(DPPC) (defect density and fusion maximum). Under such conditions the average size of PC/FA (1:2) mixed vesicles in a 1 mM suspension increases by a factor of 10 over a period of 10 min. Interbilayer fusion can also be catalyzed by the mechanically induced local membrane defects. Freshly made liposomes thus always fuse more avidly than aged vesicles. This permits estimates of the kinetics of membrane defects annihilation based on the measured temporal dependence of the maximum fusion-rate. From such studies, a quasi-exponential decay on the time scale of 1.2 h is found for the thermolabile fusogenic DPPC/ELA-COOH liposomes.

Fatty Acids↗

PubMed1994

Scanning tunneling microscopy of insulators and biological specimens based on lateral conductivity of ultrathin water films.

Scanning tunneling microscopy is based on the flow of an electrical current and thus cannot be used to directly image insulating material. It has been found, however, that a very thin film of water (about one monolayer) adsorbed to a surface exhibits a surprisingly high conductivity that is sufficient to allow scanning tunneling microscope imaging at currents below 1 picoampere. Hydrophilic insulators, such as glass and mica, can thus be imaged in humid air. The same is true for biological specimens deposited on such surfaces, as demonstrated by the scanning tunneling microscope imaging of plasmid DNA on mica.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

Solute effects on the colloidal and phase behavior of lipid bilayer membranes: ethanol-dipalmitoylphosphatidylcholine mixtures.

By means of the scanning differential calorimetry, x-ray diffractometry, and the dynamic light scattering, we have systematically studied the phase and packing properties of dipalmitoylphosphatidylcholine vesicles or multibilayers in the presence of ethanol. We have also determined the partial ternary phase diagram of such dipalmitoylphosphatidylcholine/water/ethanol mixtures. The directly measured variability of the structural bilayer parameters implies that ethanol binding to the phospholipid bilayers increases the lateral as well as the transverse repulsion between the lipid molecules. This enlarges the hydrocarbon tilt (by up to 23 degrees) and molecular area (by < or = 40%). Ethanol-phospholid association also broadens the interface and, thus, promotes lipid headgroup solvation. This results in excessive swelling (by 130%) of the phosphatidylcholine bilayers in aqueous ethanol solutions. Lateral bilayer expansion, moreover, provokes a successive interdigitation of the hydrocarbon chains in the systems with bulk ethanol concentrations of 0.4-1.2 M. The hydrocarbon packing density as well as the propensity for the formation of lamellar gel phases simultaneously increase. The pretransition temperature of phosphatidylcholine bilayers is more sensitive to the addition of alcohol (initial shift: delta Tp = 22 degrees C/mol) than the subtransition temperature (delta Ts reversible 5 degrees C/mol), whereas the chain-melting phase transition temperature is even less affected (delta Tm = 1.8 degrees C/mol). After an initial decrease of 3 degrees for the bulk ethanol concentrations below 1.2 M, the Tm value increases by 2.5 degrees above this limiting concentration. The gel-phase phosphatidylcholine membranes below Tm are fully interdigitated above this limiting concentration. The chain tilt on the fringe of full chain interdigitation is zero and increases with higher ethanol concentrations. Above Tm, some of the lipid molecules are solubilized by the bound ethanol molecules. More highly concentrated ethanol solutions (> 7 M) solubilize the phosphatidylcholine bilayers with fluid chains fully and result in the formation of mixed lipid-alcohol micelles.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1993

Specific targeting with poly(ethylene glycol)-modified liposomes: coupling of homing devices to the ends of the polymeric chains combines effective target binding with long circulation times.

One possibility for bringing drugs to their specific targets is to use the drug-laden liposomes that have been made target-specific by the attachment of appropriate proteins. Such 'directed' proteoliposomes and most other particles are rapidly removed from the bloodstream, however, by the mononuclear phagocytes in the liver and spleen. This causes suboptimal drug accumulation at the target site. Coating the liposome surface with poly(ethylene glycol) (PEG) may prolong the circulation time of liposomes. Using plasminogen as a homing device we have shown that the PEG-modified liposomes with such a homing device coupled to the ends of the long PEG chains may combine long vesicle circulation times in the blood with high target binding capability. The PEG-coated proteoliposomes with homing devices attached at the very bilayer surface, on the contrary, are longlived but have only little or no capability to bind to their targets.

Animals↗

PubMed1993

Molecular mechanism of the lipid vesicle longevity in vivo.

An important, if not the chief, condition for the prolongation of the circulation times of lipid vesicles in vivo is the suppression of macromolecular adsorption onto the surface of such vesicles. This adsorption can be prevented very efficiently by a zone of suitably designed and mobile steric hindrances near the lipid layer surface. Lipid vesicles with such a surface coat, cryptosomes, thus circulate in blood for very long periods of time after systemic applications. Lipid vesicles composed of phosphatidylcholine molecules and of suitable polyoxyethylene (PEG) derivatives of phosphatidylethanolamine, for example, remain in the blood circulation 8-10-times longer than standard liposomes made of phosphatidylcholine only: in mice the half-lives of the former and latter vesicles, after an i.v. administration, are approx. 0.6 h and between 5.9 and 13.8 h, respectively. Vesicle longevity is not destroyed by the phosphatidylcholine chains fluidity. Vesicles consisting of a mixture of distearoylphosphatidylethanolamine-PEG (DSPE-PEG) with distearoylphosphatidylcholine or cryptosomes made of DSPE-PEG and soy-bean phosphatidylcholine, consequently, have a very similar fate in vivo. Furthermore, the cryptosome longevity is not affected directly by the presence of the net charges on the lipid membranes and is little sensitive to the details of the group coupling the PEG-headgroups and the lipidic (hydrophobic) anchor. However, the life-time and the distribution of the stabilized lipid vesicles in vivo depend quite sensitively on the surface density of the sterically active headgroups; often (if not always) the resistance to plasma components adsorption as well as the resulting longevity in vivo both show a maximum near the same lipid/stabilizer molar ratio. Optimum bilayer composition may differ for the different combinations of the main and sterically active membrane components. Its position is probably determined by the variations in the molecular mobility and the effective surface-coverage effects: both must be sufficiently high for the vesicle phagocytosis and accumulation in the reticulohystiocytic system to be suppressed. On the contrary, the bilayer surface hydrophilicity, which hitherto has been believed to be of paramount importance for the liposome longevity in vivo, is per se not relevant for the biological fate of the lipid vesicles, provided that this hydrophilicity exceeds some minimum value.

Adsorption↗

PubMed1992

The mechanism of the solute-induced chain interdigitation in phosphatidylcholine vesicles and characterization of the isothermal phase transitions by means of dynamic light scattering.

A new method is introduced for the detection of chain interdigitation in phospholipid bilayers. The same method is used to measure the hydrocarbon tilt in the dipalmitoylphosphatidylcholine membranes as a function of the bulk concentration of the interdigitation-inducing solutes, such as ethanol. The hydrocarbon tilt in the phosphatidylcholine bilayers is demonstrated to be limited to angles below approx. 51 degrees. The need for higher tilt values leads to bilayer interdigitation. Solute-induced chain interdigitation is shown to be a cooperative process provoked by the excessively large lateral repulsion in the interfacial region and the concomitant excessive chain tilt. Ethanol-induced phosphatidylcholine interdigitation, for example, proceeds via interdigitated domains formation and finally gives rise to the bilayers with fully intercalated chains tilted by at least 30 degrees (and sometimes as much as 50 degrees) with respect to the membrane normal.

Ethanol↗

PubMed1992

Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force.

Gradients across the outer skin layers may result in fields enforcing a lipid flow into or through the intact skin surface provided that lipids are applied in the form of special vesicles. The osmotic gradient, for example, which is created by the difference in the total water concentrations between the skin surface and the skin interior, provides one possible source of such driving force. It is sufficiently strong to push at least 0.5 mg of lipids per hour and cm2 through the skin permeability barrier in the region of stratum corneum. The lipid concentration gradient, on the contrary, does not contribute much to the lipid penetration into dermis. Occlusion, therefore, is detrimental for the vesicle penetration into intact skin.

Animals↗

PubMed1992

Noninvasive percutaneous induction of topical analgesia by a new type of drug carrier, and prolongation of local pain insensitivity by anesthetic liposomes.

We studied the duration of action and permeability of common analgesics and local anesthetics applied dermally via new carriers--transfersomes--in rats and humans. The therapeutic potential of analgesic transfersomes was evaluated in Sprague-Dawley rats subjected to heat and pressure stimuli. Results were compared with those obtained from administration of lidocaine-containing standard liposomes. In rats, subcutaneous injections of 2% lidocaine solution and of liposomal or transfersomal suspension resulted in a strong initial analgesic effect that decayed within 6-7 min. Characteristic withdrawal time is approximately 30 s. Dermally applied analgesic transfersomes, by contrast, increased heat stimulus reaction to greater than 70 s, 130% longer than in controls that received a placebo or a standard aqueous lidocaine solution. In humans, we tested two groups of nine male and female volunteers, aged between 25 and 60 yr, for pain-suppressing activity assessed by the pinprick method. Each subject received a total of 0.5 mL of a transfersomal preparation containing 7% lidocaine or 4% tetracaine over a forearm area of 9 cm. We conclude that the effectiveness of dermally applied anesthetic transfersomes is similar to that of the corresponding subcutaneous injections of similar drug quantities and that optimally designed transfersomes offer a suitable and promising means for the noninvasive treatment of local pain with direct, topical drug application.

Administration, Cutaneous↗

PubMed1991

How membrane chain-melting phase-transition temperature is affected by the lipid chain asymmetry and degree of unsaturation: an effective chain-length model.

Hydrocarbon effects on the lipid chain-melting phase-transition temperature are analyzed. The membrane fluidization temperature is shown to increase with the effective chain length, which is proportional to the thickness of the well-packed hydrocarbon region. The latter, as a rule, increases with the length of the longest ordered and aligned segment on each chain. This conclusion is independent of the cause for the reduced chain packing in membrane interior: chain unsaturation (which effectively decouples the two hydrocarbon segments disjoined by a double bond) or chain asymmetry (which causes the terminal hydrocarbon segments to lose close contact) both affect the bilayer chain-melting phase-transition temperature comparably on the effective chain-length scale. Thermodynamic consequences of the trans unsaturation are approximately 50% smaller than the effects of the double bonds in the cis conformation, owing to the smaller membrane perturbation by the former double bonds. A simple quantitative model is introduced for the analysis of the phospholipid chain-melting phase behavior. This new model permits quantitative predictions of the chain-melting transition temperature solely on the basis of the known lipid chemical composition. It also explains lipid sensitivity to the hydrocarbon type and attachment. The model agreement with the experimental data is usually better than to within 99% and thus comparable to experimental scatter, even when only a few or no adjustable parameters are used. The membrane fluidization temperature is calculated for a number of potentially interesting, also as yet unexplored, phospholipids, and the biological significance of the effective chain-length concept is discussed.

Hydrocarbons↗

PubMed1991

Polymorphism of the bilayer membranes in the ordered phase and the molecular origin of the lipid pretransition and rippled lamellae.

The lamellar-to-undulated-lamellar phase transition (L beta'----P beta', pretransition) in lipid bilayers is shown to be a phenomenon which exists only if lipid polar headgroups are sufficiently hydrated and if the interchain packing is sufficiently weak. The minimal lipid hydrophilicity and the critical amount of the lipid-bound water can be related to the lipid chain-melting transition temperature; the latter must not exceed some maximal, chainlength-dependent value if the pretransition is to exist. The minimally required amount of the lipid-bound water itself is essentially chainlength independent, however, and unaffected by the method of hydration variation: physical dehydration, hydrational competition between the lipid molecules and the substances dissolved in the aqueous subphase, or decreasing lipid headgroup polarity all affect the pretransition temperature similarly on the appropriate scale. Simple, phenomenological expressions for the evaluation of the bilayer subtransition, pretransition and chain-melting phase transition temperature as a function of the lipid chainlength are presented. They show that, even in excess water, bilayers will tend to undulate only as long as each of the two identical lipid chains will contain between 12 +/- 1 and 22 +/- 1 carbon atoms, the P beta-phase region for the less polar lipids being as a rule narrower. To get a theoretical means for quantitatively studying the effects of the lipid hydration on the bilayer pretransition, an interaction-balance method is proposed for describing undulated membranes at the molecular level. This is based on comparing the free-energy gain from the increased headgroup hydration with the free-energy loss caused by the reduced chain-chain attraction upon ripple formation. A rationale is thus found for scaling the pretransition temperature in terms of the hydration-induced chain-melting phase transition shift or of the lipid surface hydrophilicity. Within the framework of such a model the recently reported (de)hydration dependence of the bilayer-undulation period is reproduced with reasonable accuracy. Furthermore, it is estimated that at least 12 +/- 2 water molecules must be associated with each lipid head for the bilayer undulation to be feasible. The closer the system is to this boundary condition the longer is the repeat-distance for the surface undulations and the less stable is the undulated bilayer phase.

Gels↗

PubMed1991

Isothermal lipid phase transitions.

In liotropic lipid systems phase transitions can be induced isothermally by changing the solvent concentration or composition; alternatively, lipid composition can be modified by (bio)chemical means. The probability for isothermal phase transitions increases with the decreasing transition entropy; it is proportional to the magnitude of the transition temperature shift caused by transformation-inducing system variation. Manipulations causing large thermodynamic effects, such as lipid (de)hydration, binding of protons or divalent ions and macromolecular adsorption, but also close bilayer approach are, therefore, likely to cause structural lipid change(s) at a constant temperature. Net lipid charges enhance the membrane susceptibility to salt-induced isothermal phase transitions; a large proportion of this effect is due to the bilayer dehydration, however, rather than being a consequence of the decreased Coulombic electrostatic interactions. Membrane propensity for isothermal phase transitions, consequently, always increases with the hydrophilicity of the lipid heads, as well as with the desaturation and shortening of the lipid chains. Upon a phase change at a constant temperature, some of the interfacially bound solutes (e.g. protons or calcium) are released in the solution. Membrane permeability and fusogenicity simultaneously increase. In mixed systems, isothermal phase transitions, moreover, may result in lateral phase separation. All this opens up ways for the involvement of isothermal phase transitions in the regulation of biological processes.

Lipid Bilayers↗

PubMed1990

Liposomes for the sustained drug release in vivo.

New lipidic carriers suitable for the sustained drug release in vivo are presented. They consist of middle sized, compact phospholipid vesicles with one or up to few lipid bilayers which are sterically stabilized with a small amount of large-head phospholipids. As an example, phosphatidylcholine (PC) liposomes casted with up to 10 mol% of phosphatidylethanolamine with a covalently attached polyethyleneglycol 5000 headgroup (PE-PEG) are discussed. Such vesicles exhibit a very long circulation time after an i.v. administration in mice; the improvement over pure phosphatidylcholine liposomes within the first 24 h exceeds 8000%, at this point nearly 25% of the applied PE-PEG liposomes being still in the circulation. This advantage is a consequence of reduced phagocytosis of the lipidic carriers, as shown by an in vitro assay with blood monocyte cells in the flow cytometric experiments. For example, after 6 h incubation with THP-1 monocyte cells in human plasma the difference between the uptake of standard distearoylphosphatidylcholine (DSPC) and novel liposomes containing 10% distearoylphosphatidylethanolamine-PEG is by 1000%. Vesicles with 2.5 mol% DSPE-PEG are also taken-up via phagocytosis relatively slowly. But the latter vesicles, moreover, retain most of the enclosed model-drug carboxyfluorescein after an incubation in plasma. The rate of permeation of the encapsulated substance from such DSPE-PEG liposomes is below 2.4% per h. This is by approximately a factor of two less than for pure DSPC liposomes; vesicles with a higher PE-PEG content are inferior in this respect. Long circulation time and high retention of the newly developed liposomes open up ways for the future systemic use as such stabilized drug carriers for the therapeutic applications in vivo.

Drug Carriers↗

PubMed1990

Membrane electrostatics.

In conclusion, charged membrane together with their adjacent electrolyte solution form a thermodynamic and physico-chemical entity. Their surfaces represent an exceptionally complicated interfacial system owing to intrinsic membrane complexity, as well as to the polarity and often large thickness of the interfacial region. Despite this, charged membranes can be described reasonably accurately within the framework of available theoretical models, provided that the latter are chosen on the basis of suitable criteria, which are briefly discussed in Section A. Interion correlations are likely to be important for the regular and/or rigid, thin membrane-solution interfaces. Lateral distribution of the structural membrane charge is seldom and charge distribution perpendicular to the membranes is nearly always electrostatically important. So is the interfacial hydration, which to a large extent determines the properties of the innermost part of the interfacial region, with a thickness of 2-3 nm. Fine structure of the ion double-layer and the interfacial smearing of the structural membrane charge decrease whilst the surface hydration increases the calculated value of the electrostatic membrane potential relative to the result of common Gouy-Chapman approximation. In some cases these effects partly cancel-out; simple electrostatic models are then fairly accurate. Notwithstanding this, it is at present difficult to draw detailed molecular conclusions from a large part of the published data, mainly owing to the lack of really stringent controls or calibrations. Ion binding to the membrane surface is a complicated process which involves charge-charge as well as charge-solvent interactions. Its efficiency normally increases with the ion valency and with the membrane charge density, but it is also strongly dependent on the physico-chemical and thermodynamic state of the membrane. Except in the case of the stereospecific ion binding to a membrane, the relatively easily accessible phosphate and carboxylic groups on lipids and integral membrane proteins are the main cation binding sites. Anions bind preferentially to the amine groups, even on zwitterionic molecules. Membrane structure is apt to change upon ion binding but not always in the same direction: membranes with bound ions can either expand or become more condensed, depending on the final hydrophilicity (polarity) of the membrane surface. The more polar membranes, as a rule, are less tightly packed and more fluid. Diffusive ion flow across a membrane depends on the transmembrane potential and concentration gradients, but also on the coulombic and hydration potentials at the membrane surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Phosphatidylcholine-fatty acid membranes. I. Effects of protonation, salt concentration, temperature and chain-length on the colloidal and phase properties of mixed vesicles, bilayers and nonlamellar structures.

The phase and colloidal properties of phosphatidylcholine/fatty acid (PC/FA) mixed vesicles have been investigated by optical methods, acid-base titration, and theoretically as a function of temperature (5-80 degrees C), molar lipid ratio (0-1), lipid chain length (C14-C18), headgroup ionization (1.5 less than or equal to pH less than or equal to 10), vesicle concentration (0.05-32 mumol vesicle.dm-3, and ionic strength (0.005 less than or equal to J less than or equal to 0.25). Increasing the fatty acid concentration in PC bilayers causes the phase transition temperatures (at 4 less than or equal to pH less than or equal to 5) to rise until, for more than 2 FA molecules per PC molecule, the sample turbidity exhibits only two transitions corresponding to the chain-melting of the 1:2 stoichiometric complexes of PC/FA, and pure fatty acid. The former transition is into a nonlamellar phase and is accompanied by extremely rapid vesicle aggregation (with association rates on the order of Ca approximately 10(7) dm3.mol-1.s-1) and massive lipid precipitation. Fluid-phase vesicles with less than 2 FA per PC associate much more slowly (Ca approximately 10(3) dm3.mol-1.s-1), their aggregation being comparable to that of the ordered-phase liposomes. Under no conditions was the relation between the fatty acid concentration and the vesicle association rate for the fluid-phase vesicles linear. In contrast to the X-ray diffraction data, optical measurements reveal a 'pretransitional region' between the chain-melting temperature of the PC component and the temperature at which the gross transformation into a nonlamellar phase sets in. This is seen for all lipid mixtures investigated. On the relative temperature scale, lipids with different chain lengths behave qualitatively similarly; however, the effective association constants determined for samples of constant lipid concentration seem to decrease somewhat with the number of CH2 groups per chain. Fatty acid protonation, which yields electrically neutral bilayers, invariably increases the rate of vesicle association; we have measured, for example, Ca approximately 10(2) at pH approximately 7 and Ca approximately 10(7) dm3.mol-1.s-1 at pH approximately 4). Protonation of the phosphatidylcholine phosphate groups, which causes a net positive charge to accumulate on the lipid vesicles, initially increases (Ca approximately 10(8) dm3.mol-1.s-1) but ultimately decreases (Ca approximately 10(7) dm3.mol-1.s-1) the rate of association between PC/FA (1:2) mixed vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Phenomena↗

PubMed1987

How membrane chain melting properties are regulated by the polar surface of the lipid bilayer.

The principle of regulation of various membrane properties by the hydrocarbon membrane interior is now well understood. The mechanism by which the interfacial membrane region including aqueous solution affects the state of the lipid bilayer matrix, however, is as yet unclear, despite its great biological and physiological significance. Data and analysis presented in this paper show that apart from the lipid chain type, length, and degree of unsaturation the main factors determining the characteristics of lipid membranes are surface polarity and interfacial hydration. These incorporate the effects of head group dipole and multipole moments as well as the head group ability for hydrogen bonding and can account for most of the changes in the physicochemical membrane state caused by the lipid head group structure, bulk pH value, salt content, solute adsorption, etc. The effects of membrane potential are much less, only 10-30% of the former. Variations in hydration thus not only govern the short- and medium-range intermolecular and intermembrane interactions but also provide a fast and energetically inexpensive regulatory mechanism for lipid membranes to adapt their characteristics, at least locally or transiently, to new requirements.

Lipid Bilayers↗

PubMed1985

Hydration of noncharged lipid bilayer membranes. Theory and experiments with phosphatidylethanolamines.

Calorimetric measurements have been made on the thermodynamics of the chain-melting phase transition of saturated diacylphosphatidylethanolamines, with chains containing 12-20 carbons, as a function of water content. The transition temperature, Tt, and the transition enthalpy, and entropy all decrease with an increase in water content; however, the effect on Tt lessens with an increase in chainlength. These results are compared with a theoretical description of lipid hydration in terms of the interlamellar water polarization (i.e., modified water structure) in the interbilayer region. The measured free energy, enthalpy and entropy of the transition and the transition temperature have an approximate hyperbolic tangent dependence on water content, infinity tanh (dw/2 xi), where dw is the interlamellar water-layer thickness and xi approximately equal to 0.25 nm is the water-order correlation length, in agreement with the theory. Auxiliary x-ray diffraction experiments yield results on the repulsive hydration forces between lipid lamellae consistent with the theory, and allow an estimate of the water orienting potential of the interface. The molecular origin of this potential is discussed in electrostatic terms, and the values of its associated molecular parameters are found to yield the right size of hydrational thermodynamic quantities. The theory thus provides an integrated, clear, and simple approach to the hydration properties of lipid membranes.

Biophysical Phenomena↗