Membrane lipid phase behaviour

Tsvetkova, N.M., and P.J. Quinn (1994). Compatible solutes modulate membrane lipid phase behaviour. In Temperature Adaptation of Biological Membranes, pp. 49-61, ed. A.R. Cossins. London Portland Press. 

It is important for the theoretical understanding of the formation of various topologies that these aggregates have entropic contributions on the scale of the objects, i.e. on a much larger scale than set by the molecules. These cooperative entropic effects should be included in the overall Helmholtz energy, and they are essential to describe the full phase behaviour. It is believed that the mechanical parameters discussed above kc,k and J0, control the phase behaviour, where it is understood that these quantities may, in principle, depend on the overall surfactant (lipid) concentration, i.e. when the membranes are packed to such a density that they strongly interact. 

The link from lipid properties to mechanical properties of the bilayers is now feasible within the SCF approach. The next step is to understand the phase behaviour of the lipid systems. It is likely that large-scale (3D) SCF-type calculations are needed to prove the conjectures in the field that particular values of the Helfrich parameters are needed for processes like vesicle fusion, etc. In this context, it may also be extremely interesting to see what happens with the mechanical parameters when the system is molecularly complex (i.e. when the system contains many different types of molecules). Then there will be some hope that novel and deep insights may be obtained into the very basic questions behind nature s choice for the enormous molecular complexity in membrane systems. 

Thewalt, J. et al., Models of stratum corneum intercellular membranes the sphingolipid headgroup is a determinant of phase behaviour in mixed lipid dispersions, Biochem. Biophys. Res. Commun., 188, 1247, 1992. 

Brandenburg, K., Blume, A. Investigations into the thermotropic phase behaviour of natural membranes extracted from Gram-negative bacteria and artificial membrane systems made from lipopolysaccharides and free lipid A. Thermochim Acta 119 (1987) 127-142. 

For this purpose liposomes are used as lipid phase. Unilamellar liposomes are artificial lipid bilayer vesicles. They can be considered as real model bilayer membranes as they ideally consist of a circular bilayer membrane. The hydrophobic acyl chains are assembled in the hydrophobic core of the liposome whereas the hydrophilic head groups point to the water in the inside and outside of the vesicle. Liposomes can be produced from a variety of lipids and from mixtures of lipids. This possibility allows studying the influence of membrane constituents on the partition of solutes. Kramer et al. (1997) studied the influence of the presence of free fatty acids in membranes on the partition behaviour of propranolol. The influence on a-Tocopherol in membranes on the partition behaviour of desipramine has been reported recently (Marenchino et al. 2004) using a liposome model. 

Lewis RNAH, McElhaney RN. The mesomorphic phase behaviour of lipid bilayers. In The Structure of Biological Membranes. Yeagle PE, ed. 1991. CRC Press, Boca Raton, FL. pp. 73-155. Ipsen JH, Karlstrom G, Mouritsen OG, Wennerstrom H, Zuk-ermann MJ. Phase equilibria in phosphatidylcholine-cholesterol system. Biochim. Biophys. Acta 1987 905 162-172. 

The phosphorescence of trivalent cations (as analogues of Ca ) is also widely used in binding studies. The photobinding of phenothiazine derivatives has been studied for different types of biological membranes. The specificity of binding is low, although general, and can be used to identify and localize membrane proteins. The influence of Ca " and phase behaviour in synaptosomal lipids have been examined by the steady-state fluorescence polarization of A fluorescent probe of the tumour promoter phorbol... 

Besides the asymmetry between monolayers in cytomembranes, two of the more obvious differences between cubic phases and membranes are the unit cell size and the water activity. It has been argued that tire latter must control the topology of the cubic membranes [15], and hence tiiat the cubic membrane structures must be of the reversed type (in the accepted nomenclature of equilibrium phase behaviour discussed in Chapters 4 and 5 type II) rather than normal (type I). All known lipid-water and lipid-protein-water systems that exhibit phases in equilibrium with excess water are of the reversed type. Thus, water activity alone cannot determine the topology of cubic membranes. Cubic phases have recently been observed with very high water activity (75-90 wt.%), in mixtures of lipids [127], in lipid-protein systems [56], in lipid-poloxamer systems [128], and in lipid A and similar lipopolysaccharides [129,130]. 

What are the functions, if any, of the cubic membranes It may be that cubic membranes are but an inevitable self-assembled product of the complex molecular soup of lipids and proteins the result of molecular packing considerations and inter-molecular interactions. This would be in analogy with known phase behaviour in equilibrium systems. Even though this is a very appealing solution to the long and unresolved debate about "non-lamellar" lipids in conjunction with cell membranes, we rather believe that these structural organisations have been chosen to fulfil a purpose (see, e.g. [134] and references therein for current theories, and [4] for a more comprehensive discussion), and the formation cannot be rationalised solely by molecular packing. 

Tokumasu, F, Jin, A. J., and Dvorak, J. A. 2002. Lipid membrane phase behaviour elucidated in real time by controlled environment atomic force microscopy, / Ekrfrow Microsc (Tokyo) 51,1-9. 

Differences occur with regard to the three-dimensional arrangement of the non-aqueous phases. Most biological lipids consist of membranes, in which the molecules are predominantly arranged in bilayers. The lipid phase thus has a distinct structure and restricted spatial dimensions. Because the 1-octanol phase is a bulk phase, presumably with little or no structure, organic solutes may display different activity coefficients and partitioning behaviour in 1-octanol than in membranes. The more ordered a lipid phase is - in, for example, micelles and membranes - the more important becomes the entropy, resulting in non-linearity of the relationship between the respective partition coefficients and log... 

It is not only the solubility in aqueous solutions that may affect the biopharmaceutical behaviour of an active substance. The solubility in non-polar solvents is of importance too. The solubility in a lipid phase is of relevance to the passive transport of the substance over lipid membranes, a process that plays an important role in the absorption of many drags. In order to quantify the lipophilicity of an active substance in relation to its aqueous solubility the concept of the partition coefficient was developed. The partition coefficient is defined as the quantitative distribution ratio of a dissolved substance over two immiscible liquids at equilibrium. In the pharmaceutical sciences the ratio of the concentrations in an aqueous phase (water or aqueous buffer solutions) and a lipid phase (e.g. n-octanol) is often considered. For this purpose the so called log P value has been defined. The partition coefficient between an aqueous and a lipid phase (log Pq/w value) of non-ionised substances is defined according to (16.1) ... 

THE PHASE BEHAVIOUR OF MEMBRANE LIPIDS AND THE ORGANISATION OF THE PHOTOSYNTHETIC MEMBRANE... 

PHASE BEHAVIOUR OF MEMBRANE LIPIDS The molecular species of membrane lipids including that of the photosynthetic membrane is highly complex with members of each of the major lipid classes containing fatty acyl substituents that differ in length and extent of unsaturation and position of attachment to the... 

The above discussion indicates that a knowledge of the phase behaviour of individual molecular species of lipid comprising the matrix of the thylakoid membrane of higher plant chloroplasts can be informative of the factors governing the stability of the membrane. Perhaps the most important conclusion is that the presence of non-bilayer forming lipids is not simply required to facilitate the dynamic functions such as membrane fusion etc., but also to play a role in the creation of oligomeric functional complexes of the different membrane proteins. 

Based on knowledge of the phase behaviour of membrane lipids it is possible to predict the events that accompany exposure of biological membranes to extremes of temperature. Because the destabilizing events are fundamentally different the effect of low temperature and high temperature on membrane structure and stability will be considered sepa rately. 

Cooling to temperatures below ice crystallisation results in dehydration of membranes as the bulk water freezes and solutes are zone-refined to the regions of unfreezable water at the membrane aqueous interface. Saturated solutions of electrolytes and solutes affect membrane phase behaviour by screening charges on acidic lipids which are known to be important for the overall phase behaviour of the membrane. 

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