Investigation into the fluidity of lipopolysaccharide and free lipid A membrane systems by Fourier-transform infrared spectroscopy and differential scanning calorimetry

The phase behaviour, particularly the fluidity within each phase state and the transitions between them, of lipopolysaccharides and of their lipid moiety, free lipid A, of various species of Gram-negative bacteria, especially of Salmonella minnesota and Escherichia coli, has been investigated by applying mainly Fourier-transform infrared spectroscopy and differential scanning calorimetry. For enterobacterial strains, the transition temperatures of the gel----liquid crystalline (beta----alpha) phase transition of the hydrocarbon chains in dependence on the length of the sugar moiety are highest for free lipids A (around 45 degrees C) and lowest for deep rough mutant lipopolysaccharides (around 30 degrees C). Evaluating certain infrared active vibration bands of the hydrocarbon moiety, mainly the symmetric stretching vibration of the methylene groups around 2850 cm-1, it was found that, in the gel state, the acyl chains of lipopolysaccharides and free lipid A have a higher fluidity as compared with saturated and the same fluidity as compared with unsaturated phospholipids. This 'partial fluidization' of lipopolysaccharide below the transition temperature correlates with its reduced enthalpy change at that temperature compared to phospholipids with the same chain length. The fluidity depends strongly on ambient conditions, i.e. on the Mg2+ and H+ content: higher Mg2+ concentrations and low pH values make the acyl chains of free lipid A and lipopolysaccharide preparations significantly more rigid and also partially increase the transition temperature. The influence of Mg2+ is highest for free lipid A and decreases with increasing length of the sugar side chain within the lipopolysaccharide molecules, whereas the effect of a low pH is similar for all preparations. At basic pH, a fluidization of the lipopolysaccharide and lipid A acyl chains and a decrease in transition temperature take place. Free lipid A and all investigated rough mutant lipopolysaccharides exhibit an extremely strong lyotropic behaviour in the beta----alpha melting enthalpy but not in the value of the transition temperature. The phase transition is distinctly expressed only at water concentrations higher than 50-60%. A further increase of the water content still leads to an increase in the phase-transition enthalpy, particularly for lipopolysaccharides with a more complete sugar moiety. The fluidity of the hydrocarbon chains is shown to be an important parameter with respect to the expression of biological activities.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of the phase transition on the hydration and electrical conductivity of phospholipids.

Adsorption isotherms for various saturated phosphatidylcholines have been obtained. Lipids above and below their phase transition temperature differ only in the amount of water adsorbed and not in the nature of their adsorption isotherms. Cholesterol has an effect similar to that of increasing unsaturation in the hydrocarbon chains. Decreasing the length of the hydrocarbon chains for lipids below their phase transition temperature has no effect on the isotherms. If the chain length is short enough so that the lipids are above their transition temperature, however, a large increase in water adsorption occurs. All of the phospholipids exhibit a rapid increase of electrical conductivity for a few water molecules adsorbed per lipid molecule. All of the phospholipids show a saturation in conductivity at greater amounts of adsorbed water; the shape of the saturation region depends on whether the lipids are above or below their phase transition temperature. The activation energy for the electrical conductivity process depends on whether the hydrated lipids are in the "liquid-like" of the crystalline state, being lower for phospholipids in the liquid-like state. If the lipids are hydrated above their phase transition temperatures, their activation energies are lower than if they are hydrated below the transition temperature. Cholesterol lowers the activation energy. The phosphatidylcholines can be characterized by different activation energies, depending both upon their physical state and the presence of unsaturation in their hydrocarbon chains.     

Area per lipid and acyl length distributions in fluid phosphatidylcholines determined by (2)H NMR spectroscopy

Deuterium ((2)H) NMR spectroscopy provides detailed information regarding the structural fluctuations of lipid bilayers, including both the equilibrium properties and dynamics. Experimental (2)H NMR measurements for the homologous series of 1, 2-diacyl-sn-glycero-3-phosphocholines with perdeuterated saturated chains (from C12:0 to C18:0) have been performed on randomly oriented, fully hydrated multilamellar samples. For each lipid, the C-D bond order parameters have been calculated from de-Paked (2)H NMR spectra as a function of temperature. The experimental order parameters were analyzed using a mean-torque potential model for the acyl chain segment distributions, and comparison was made with the conventional diamond lattice approach. Statistical mechanical principles were used to relate the measured order parameters to the lipid bilayer structural parameters: the hydrocarbon thickness and the mean interfacial area per lipid. At fixed temperature, the area decreases with increasing acyl length, indicating increased van der Waals attraction for longer lipid chains. However, the main effect of increasing the acyl chain length is on the hydrocarbon thickness rather than on the area per lipid. Expansion coefficients of the structural parameters are reported and interpreted using an empirical free energy function that describes the force balance in fluid bilayers. At the same absolute temperature, the phosphatidylcholine (PC) series exhibits a universal chain packing profile that differs from that of phosphatidylethanolamines (PE). Hence, the lateral packing of phospholipids is more sensitive to the headgroup methylation than to the acyl chain length. A fit to the area per lipid for the PC series using the empirical free energy function shows that the PE area represents a limiting value for the packing of fluid acyl chains.     

Hydrocarbon chain packing and molecular motion in phospholipid bilayers formed from unsaturated lecithins. Synthesis and properties of sixteen positional isomers of 1,2-dioctadecenoyl-sn-glycero-3-phosphorylcholine.

Isomers of cis-octadecenoic acid, with the double bond in each position in the hydrocarbon chain, were used to synthesize the corresponding 1,2-diacyl-sn-glycero-3phosphorylcholines (lecithins). Differential thermal analysis of the lecithins, as a function of water content, permitted evaluation of the limiting transition temperature (Tc) of each isomer. Values of Tc plotted against double bond position fell on a smooth curve with a minimum at minus 22 degrees for the dioctadec-9'-enoyl compound. The presence of a "pretransition" endotherm in differential thermal analysis of 1,2-dioctadec-15'-and 1,2-dioctadec-16'-enoyl-sn-glycero-3-phosphorylcholine implies the existence of two beta crystalline forms. This was not observed with any of the other lecithins. Enthalpy and entropy data were then obtained from differential scanning calorimetry measurements. Values of delta H were lower (7.6 plus or minus 0.1 kcal mol- minus 1) when the center of unsaturation was near the middle of the hydrocarbon chain than they were (9.6 kcal mol- minus 1) when the center of unsaturation was close to either end of the chain. However, values of delta S showed no consistent variation with double bond position. Four positional isomers of 1-octadec-cis-enoyl-2-octadecanoyl-sn-glycero-3-phosphorylcholine were synthesized. With the double bond near the middle of the chain or close to the terminal group, the Tc values of the mixed acid lecithins were higher than those of the corresponding dioctadecenoyl lecithins. 13-C nuclear magnetic resonance relaxation measurements were used to obtain information about chain motion of selected 1,2-dioctadec-cis-enoyl-sn-glycero-3-phosphorylcholines at a temperature (52 degrees) above the Tc values. Spin-lattice relaxation times of the resolved resonances indicated that location of double bonds near the middle, as compared to either end, of the hydrocarbon chain favors enhanced molecular motion along the length of the chins and especially at the terminal methyl end. In the gel state, the minimum interaction potential energy of hydrocarbon chains in bilayers formed from dioctadecenoyl lipids appears to be minimized by localization of the double bond near the middle of the chains. It is suggested that in the case of homogeneous chains the double bond primarily affects the cooperativity of interactions and has very little steric effect on van der Waals' contacts. By contrast, in bilayers of mixed lecithins, with heterogeneous chains, the steric effect may become dominant, depending on double bond position. These differences in chain packing in the gel state are promulgated beyond the phase transition to the liquid crystalline state as an enhancement of chain motion as the temperature rises above Tc.     

Simulation of Chain-length Partitioning in a Microfabricated Channel via Entropic Trapping

A molecular simulation approach has been used to investigate the mechanism of entropic trapping for model linear DNA molecules as they go from a deep channel to a shallow channel driven by an electric field. In such a system, a molecule whose radius of gyration is larger than the gap of the shallow channel will tend to get temporarily trapped at its entrance. The free energy of the molecules as a function of chain position and the trapping times were obtained via Monte Carlo simulations. In weak to moderate electrical fields, the free energy barrier for escape ( F max increases with chain length approaching a plateau value; in a strong electrical field, ( F max exhibits a mild decreasing trend with chain length. At weak electric fields, shorter chains escape faster than longer chains because of their lower associated ( F max . At moderate and strong fields, longer chains escape faster than shorter ones because, in the absence of significant differences in ( F max , larger chains access a larger entrance area to the narrow channel; these results are in agreement with reported experimental observations. Preliminary results on the effect of chain branching on the escape rate are also presented.     

Accommodation of hydroxyl groups and their hydrogen bond system in a hydrocarbon matrix

From data of sisingle crystal analysis of 12-D-hydroxyoctadecanoic acid methyl ester principles for the incorporation of hydroxyl groups into a hydrocarbon chain matrix can be deduced. In the crystalline compound infinite hydrogen bond systems are accommodated in an orthorhombic perpendicular (O) chain arrangement. The O hydrocarbon subcell is expanded towards a hexagonal packing pattern, allowing more space and optimal geometry for the hydrogen bond system. The arrangement of the bond system in the O subcell requires that hydrogen bonded carbon chains carry alternatingly hydroxyl roups with opposite configuration. For the enantiomeric compound this requirement is met by a head to tail packing of molecules in a single layer arrangement. The corresponding racemates on the other hand pack head to head in double layers as confirmed by X-ray powder and IR studies. In monolayers both enantiomers and racemates behave identicalyy. The hydrogen bonding of the hydroxyl groups apparently leads to the formation of lipid clusters, in which the geometric conditions for both a close packing of hydrocarbon chains and the formation of an extensive hydrogen bond system do not exist.     

In vitro hydrolysis of poly(l-lactide) crystalline residues as extended-chain crystallites: II. Effects of hydrolysis temperature

The effects of hydrolysis temperature on the hydrolysis behavior and mechanism of poly(l-lactide) crystalline residues or extended-chain crystallites were investigated in phosphate-buffered solution (50-97 degrees C), using gel permeation chromatography and differential scanning calorimetry (DSC). The hydrolysis of the crystalline residues proceeded from their surface composed of very short chains with a free end along the chain direction, irrespective of hydrolysis temperature, but the hydrolysis from their lateral surface could not be traced. The activation energy of hydrolysis for the crystalline residues (extended-chain crystallites) was evaluated to be 18.0 kcal mol(-1) (75.2 kJ mol(-1)). The monotonic melting temperature (T(m)) and crystallinity decreases occurred after their initial very small increases, excluding the monotonic crystallinity decrease at 97 degrees C with no initial increase. The T(m) decrease reflects the decreased thickness of the crystalline residues. The equilibrium T(m) of the crystalline residues (extended-chain crystallites) was estimated to be 464.5-464.9 K. The free energy values for the surface composed of very short chains with a free end, which are neighboring the air (or nitrogen during DSC scanning), were calculated to be 55.6-56.4 erg cm(-2) for heat of fusion per unit mass = 135 J g(-1). The obtained surface free energy values are significantly higher than that for the surface composed of folding chains, tie chains, and the chains with a free end, which are neighboring the same kind of amorphous chains (39.9 erg cm(-2)).     

Chain ordering in liquid crystals: II. Structure of bilayer membranes

The ordering of the hydrocarbon chain interior of bilayer membranes has been calculated using the molecular field approximation developed in previous work on liquid crystals. Different statistical averages are evaluated by exact summation over all conformations of a single chain in the field due to neighboring molecules. The internal energy of each conformation, as well as contributions arising from interaction with the molecular field and from a lateral pressure on the chain have been included.The results describe properties of both lipid monolayers and bilayers. For monolayers, the calculated pressure-area relationships are in good agreement with experimental observations. The order parameter for hydrocarbon chains in bilayers (or monolayers) as a function of temperature, lateral pressure and position along the chain, is shown and compared with the available NMR data. Combining the results of calculation and NMR measurements we obtain the value for intrinsic lateral pressure within bilayer membranes, in excellent agreement with direct measurements on surface monolayers.The calculation also gives average length of hydrocarbon chains, thermal expansion coefficient and fraction of bonds in gauche conformations. The effect of cholesterol and proteins within the bilayer is qualitatively described, and the contribution of the bilayer interior to membrane elasticity is determined.     

The effect of cholesterol on the structure of phosphatidylcholine bilayers

The effect of cholesterol on the structure of phosphatidylcholine bilayers was investigated by X-ray diffraction methods. Electron density profiles at 5 Å resolution along with chain tilt and chain packing parameters were obtained and compared for phosphatidylcholine/cholesterol bilayers and for pure phosphatidylcholine bilayers in both the gel and liquid crystalline states. The cholesterol in the bilayer was localized by noting the position of discrete elevations in the electron density profiles. Cholesterol can either increase or decrease the width of the bilayer depending on the physical state and chain length of the lipid before the introduction of cholesterol. For saturated phosphatidylcholines containing 12–16 carbons per chain, cholesterol increases the width of the bilayer as it removes the chain tilt from gel state lipids or increases the trans conformations of the chains for liquid crystalline lipids. However, cholesterol reduces the width of 18 carbon chain bilayers below the phase transition temperature as the long phospholipid chains must deform or kink to accomodate the significantly shorter cholesterol molecule. Although cholesterol has a marked effect on hydrocarbon chain organization, it was found that, within the resolution limits of the data, the phosphatidylcholine head group conformation is unchanged by the addition of cholesterol to the bilayer. The head group is oriented parallel to the plane of the bilayer for phosphatidylcholine in the gel and liquid crystalline states and this orientation is not changed by the addition of cholesterol.     

Induction of protein-like molecular architecture by monoalkyl hydrocarbon chains

Numerous approaches have been described for creating relatively small folded biomolecular structures. "Peptide-amphiphiles," whereby monoalkyl or dialkyl hydrocarbon chains are covalently linked to peptide sequences, have been shown previously to form specific molecular architecture of enhanced stability. The present study has examined the use of monoalkyl hydrocarbon chains as a more general method for inducing protein-like structures. Peptide and peptide-amphiphiles have been characterized by CD and one- and two-dimensional nmr spectroscopic techniques. We have examined two structural elements: alpha-helices and collagen-like triple helices. The alpha-helical propensity of a 16-residue peptide either unmodified or acylated with a C(6) or C(16) monoalkyl hydrocarbon chain has been examined initially. The 16-residue peptide alone does not form a distinct structure in solution, whereas the 16-residue peptide adopts predominantly an alpha-helical structure in solution when a C(6) or C(16) monoalkyl hydrocarbon chain is N-terminally acylated. The thermal stability of the alpha-helix is greater upon addition of the C(16) compared with the C(6) chain, which correlates to the extent of aggregation induced by the respective hydrocarbon chains. Very similar results are seen using a 39-residue triple-helical model peptide, in that structural thermal stability (a) is increasingly enhanced as alkyl chain length is increased and (b) correlates to the extent of peptide-amphiphile aggregation. Overall, structures as diverse as alpha-helices, triple helices, and turns/loops have been shown to be induced and/or stabilized by alkyl chains. Increasing alkyl chain length enhances stability of the structural element and induces aggregates of defined sizes. Hydrocarbon chains may be useful as general tools for protein-like structure initiation and stabilization as well as biomaterial modification.     

Analysis of brush-particle interactions using self-consistent-field theory

Non-specific protein adsorption can be reduced by attaching polymer chains by one end to a sorbent surface. End-grafted polymer modified surfaces have also found application in size-based chromatographic bioseparations. To better understand how to tailor surfaces for these applications, a numerical SCF model has been used to calculate theoretical results for the polymer density distribution of interacting polymer chains around a solute particle positioned at a fixed distance from a surface. In addition, the excess energy required to move the particle into the polymer chains (interaction energy) is calculated using a statistical mechanical treatment of the lattice model. The effect of system variables such as particle size, chain length, surface density and Flory interaction parameters on density distributions and interaction energies is also studied. Calculations for the interaction of a solute particle with a surface covered by many polymer chains (a brush) show that the polymer segments will fill in behind the particle quite rapidly as it moves toward the surface. When there is no strong energetic attraction between the polymer and solute we predict that the interaction energy will be purely repulsive upon compression due to losses in conformational entropy of the polymer chains. Above a critical chain length, which depends upon particle size, a maximum in the force required to move the particle toward the surface is observed due to an engulfment of the particle as chains attempt to access the free volume behind the particle. If an attraction exists between the polymer and solute, such that a minimum in the interaction energy is seen, the optimum conditions for solute repulsion occur at the highest surface density attainable. Long chain length can lead to increased solute concentration within the polymer layer due to the fact that an increased number of favourable polymer–solute contacts are able to occur than with short chains at a similar entropic penalty.     

Relay model of lipid peroxidation in biological membranes

The present study examines the evidence for the important role of free radicals, localized on carbon atoms of the hydrocarbon chains, in lipid peroxidation. These radicals show a great inter- and intramolecular mobility in membranes by the way of relay-transfer (isomerisation). The sequence of intermediate steps of shift of free radicals in membranes with correction for molecular organization of the hydrocarbon zone of membranes, the intramembrane localization of unsaturated links and the gradient of mobility of the hydrocarbon chains are described. The effect of inhibitors in lipid peroxidation are interpreted in terms of decay of hydrocarbon free radicals as a result of its interaction with the antioxidant molecules. The natural antioxidants having a side chain (such as tocopherols) may be regarded as a some kind of "channel" through which free radicals leave the hydrocarbon moiety of the membrane. The processes of lipid peroxidation in membranes are subjected to a great extent to the requirements of the theory of oxidation of solid polymers and hydrocarbons.     

Phase diagrams for a model of a lipid monolayer

A microscopic model of a lipid monolayer is proposed. It includes, within a single scheme, the following factors which are considered to be essential in phase transitions in lipid systems: formation of gauche rotamers, interactions between polar heads, interactions between hydrocarbon chains (depending on their conformation) and changes in the energy of the system due to a directional ordering of the chains. Phase diagrams are constructed and discussed and it is shown how the phase diagrams are modified by alterations of these parameters and the length of the hydrocarbon chains.     

Measurement of chain tilt angle in fully hydrated bilayers of gel phase lecithins.

The tilt angle theta tilt of the hydrocarbon chains has been determined for fully hydrated gel phase of a series of saturated lecithins. Oriented samples were prepared on glass substrates and hydrated with supersaturated water vapor. Evidence for full hydration was the same intensity pattern of the low angle lamellar peaks and the same lamellar repeat D as unoriented multilamellar vesicles. Tilting the sample permitted observation of all the wide angle arcs necessary to verify the theoretical diffraction pattern corresponding to tilting of the chains towards nearest neighbors. The length of the scattering unit corresponds to two hydrocarbon chains, requiring each bilayer to scatter coherently rather than each monolayer. For DPPC, theta tilt was determined to be 32.0 +/- 0.5 degrees at 19 degrees C, slightly larger than previous direct determinations and considerably smaller than the value required by recent gravimetric measurements. This new value allows more accurate determinations of a variety of structural parameters, such as area per lipid molecule, A = 47.2 +/- 0.5 A2, and number of water molecules of hydration, nw = 11.8 +/- 0.7. As the chain length n of the lipids was increased from 16 to 20 carbons, the parameters A and nw remained constant, suggesting that the headgroup packing is at its excluded volume limit for this range. However, theta tilt increased by 3 degrees and the chain area Ac decreased by 0.5 A2. This behavior is explained in terms of a competition between a bulk free energy term and a finite or end effect term.     

Molecular dynamics simulations of the interaction of phospholipid bilayers with polycaprolactone

The molecular interaction between common polymer chains and the cell membrane is unknown. Molecular dynamics simulations offer an emerging tool to characterise the nature of the interaction between common degradable polymer chains used in biomedical applications, such as polycaprolactone, and model cell membranes. Herein we characterise with all-atomistic and coarse-grained molecular dynamics simulations the interaction between single polycaprolactone chains of varying chain lengths with a phospholipid membrane. We find that the length of the polymer chain greatly affects the nature of interaction with the membrane, as well as the membrane properties. Furthermore, we next utilise advanced sampling techniques in molecular dynamics to characterise the two-dimensional free energy surface for the interaction of varying polymer chain lengths (short, intermediate, and long) with model cell membranes. We find that the free energy minimum shifts from the membrane-water interface to the hydrophobic core of the phospholipid membrane as a function of chain length. Finally, we perform coarse-grained molecular dynamics simulations of slightly larger membranes with polymers of the same length and characterise the results as compared with all-atomistic molecular dynamics simulations. These results can be used to design polymer chain lengths and chemistries to optimise their interaction with cell membranes at the molecular level.     

Fluid phase lipid areas and bilayer thicknesses of commonly used phosphatidylcholines as a function of temperature

The structural parameters of fluid phase bilayers composed of phosphatidylcholines with fully saturated, mixed, and branched fatty acid chains, at several temperatures, have been determined by simultaneously analyzing small-angle neutron and X-ray scattering data. Bilayer parameters, such as area per lipid and overall bilayer thickness have been obtained in conjunction with intrabilayer structural parameters (e.g. hydrocarbon region thickness). The results have allowed us to assess the effect of temperature and hydrocarbon chain composition on bilayer structure. For example, we found that for all lipids there is, not surprisingly, an increase in fatty acid chain trans-gauche isomerization with increasing temperature. Moreover, this increase in trans-gauche isomerization scales with fatty acid chain length in mixed chain lipids. However, in the case of lipids with saturated fatty acid chains, trans-gauche isomerization is increasingly tempered by attractive chain-chain van der Waals interactions with increasing chain length. Finally, our results confirm a strong dependence of lipid chain dynamics as a function of double bond position along fatty acid chains.     

Lecithin bilayers. Density measurement and molecular interactions.

Density measurement are reported for bilayer dispersions of a series of saturated lecithins. For chain lengths with, respectively, 14, 15, 16, 17, and 18 carbons per chain, the values for the volume changes at the main transition are 0.027, 0.031, 0.037, 0.040 and 0.045 ml/g. The main transition temperature extrapolates with increasing chain length to the melting temperature of polyethylene. Volume changes at the lower transition are an order of magnitude smaller than the main transition. Single phase thermal expansion coefficients are also reported. The combination of X-ray data and density data indicated that the volume changes are predominantly due to the hydrocarbon chains, thus enabling the volume vCH2 of the methylene groups to be computed as a function of temperature. From this and knowledge of intermolecular interactions in hydrocarbon chains, the change in the interchain van der Waals energy, delta UvdW, at the main transition is computed for the lecithins and also for the alkanes and polyethylene at the melting transition. Using the experimental enthalpies of transition and delta UvdW, the energy equation is consistently balanced for all three systems. This yields estimates of the change in the number of gauche rotamers in the lecithins at the main transition. The consistency of these calculations supports the conclusion that the most important molecular energies for the main transition in lecithin bilayers are the hydrocarbon chain interactions and the rotational isomeric energies, and the conclusion that the main phase transition is analogous to the melting transition in the alkanes from the hexagonal phase to the liquid phase, but with some modifications.     

Structure and interactive properties of highly fluorinated phospholipid bilayers.

Because liposomes containing fluoroalkylated phospholipids are being developed for in vivo drug delivery, the structure and interactive properties of several fluoroalkylated glycerophosphocholines (PCs) were investigated by x-ray diffraction/osmotic stress, dipole potential, and hydrophobic ion binding measurements. The lipids included PCs with highly fluorinated tails on both alkyl chains and PCs with one hydrocarbon chain and one fluoroalkylated chain. Electron density profiles showed high electron density peaks in the center of the bilayer corresponding to the fluorine atoms. The height and width of these high density peaks varied systematically, depending on the number of fluorines and their position on the alkyl chains, and on whether the bilayer was in the gel or liquid crystalline phase. Wide-angle diffraction showed that in both gel and liquid crystalline bilayers the distance between adjacent alkyl chains was greater in fluoroalkylated PCs than in analogous hydrocarbon PCs. For interbilayer separations of less than about 8 A, pressure-distance relations for fluoroalkylated PCs were similar to those previously obtained from PC bilayers with hydrocarbon chains. However, for bilayer separations greater than 8A, the total repulsive pressure depended on whether the fluoroalkylated PC was in a gel or liquid-crystalline phase. We argue that these pressure-distance relations contain contributions from both hydration and entropic repulsive pressures. Dipole potentials ranged from -680 mV for PCs with both chains fluoroalkylated to -180 mV for PCs with one chain fluoroalkylated, compared to +415 mV for egg PC. The change in dipole potential as a function of subphase concentration of tetraphenyl-boron was much larger for egg PC than for fluorinated PC monolayers, indicating that the fluorine atoms modified the binding of this hydrophobic anion. Thus, compared to conventional liposomes, liposomes made from fluoroalkylated PCs have different binding properties, which may be relevant to their use as drug carriers.     

Membrane thickness and acyl chain length

It appears reasonable to expect that the primary result of a change in the length of the acyl chains within a lipid bilayer is a similar change in the bilayer thickness. In the present communication we draw attention to the somewhat more complicated effects which are found experimentally for phosphatidylcholine bilayers as the hydrocarbon chain is varied from twelve to eighteen carbons in length. The major change in dimension which occurs with variation in acyl chain length is the area occupied per molecule rather than the bilayer thickness. The same effect is seen with solute hydrocarbon such as hexane which partition into the membrane and cause only a small variation in membrane thickness but a large increase in the molecular area of the lipid. The origin of this effect arises from the almost isotropic distribution of the additional hydrocarbon to the lipid core of the membrane.     

Energetics of hydrophobic matching in lipid-protein interactions

Lipid chain length modulates the activity of transmembrane proteins by mismatch between the hydrophobic span of the protein and that of the lipid membrane. Relative binding affinities of lipids with different chain lengths are used to estimate the excess free energy of lipid-protein interaction that arises from hydrophobic mismatch. For a wide range of integral proteins and peptides, the energy cost is much less than the elastic penalty of fully stretching or compressing the lipid chains to achieve complete hydrophobic matching. The chain length dependences of the free energies of lipid association are described by a model that combines elastic chain extension with a free energy term that depends linearly on the extent of residual mismatch. The excess free energy densities involved lie in the region of 0.5-2.0 k_BT.nm⁻². Values of this size could arise from exposure of hydrophobic groups to polar portions of the lipid or protein, but not directly to water, or alternatively from changes in tilt of the transmembrane helices that are energetically comparable to those activating mechanosensitive channels. The influence of hydrophobic mismatch on dimerization of transmembrane helices and their transfer between lipid vesicles, and on shifts in chain-melting transitions of lipid bilayers by incorporated proteins, is analyzed by using the same thermodynamic model. Segmental order parameters confirm that elastic lipid chain distortions are insufficient to compensate fully for the mismatch, but the dependence on chain length with tryptophan-anchored peptides requires that the free energy density of hydrophobic mismatch should increase with increasing extent of mismatch.