Shapes of lipids

The concept of IPMS should be considered in the future in connection with structural discussions on cubic lipid-water phases. It may be expected that all these three fundamental cubic IPMS structures really occur through the need to account for the wide variations in the shape of lipid molecules. Although the structures with the methyl end group gap located in the IPMS appears to be the most probable type, the reversed alternatives, i.e. bilayers with the gap between the polar head-groups forming the IPMS, should also be considered. 

Relations between shape of lipid molecules and structure of liquid-crystalline phases... 

The shape of lipid vesicles often deviates from a sphere and, thus, cannot be determined by interfacial tension. Already 20 years ago, W. Helfrich developed a fluid shell theory in which this shape is controlled by the curvature and, thus, by the bending rigidity of the membrane. Meanwhile, this approach has led to a very fruitful interaction of experiment and theory and, thus, to a quantitative understanding of the vesicle shape. 

Why Lipids are Different from 2.4.2 The Molecular Shape of Lipids 38... 

Theoretical models of the film viscosity lead to values about 10 times smaller than those often observed [113, 114]. It may be that the experimental phenomenology is not that supposed in derivations such as those of Eqs. rV-20 and IV-22. Alternatively, it may be that virtually all of the measured surface viscosity is developed in the substrate through its interactions with the film (note Fig. IV-3). Recent hydrodynamic calculations of shape transitions in lipid domains by Stone and McConnell indicate that the transition rate depends only on the subphase viscosity [115]. Brownian motion of lipid monolayer domains also follow a fluid mechanical model wherein the mobility is independent of film viscosity but depends on the viscosity of the subphase [116]. This contrasts with the supposition that there is little coupling between the monolayer and the subphase [117] complete explanation of the film viscosity remains unresolved. 

The difficulties in investigating the influence of permeant size on permeability arise from the fact that changes in permeant size are usually accompanied by changes in lipophilicity, with the latter effects often overshadowing the effects of permeant size alone. Xiang and Anderson studied the effects of lipid chain packing and permeant size and shape on permeability across lipid bilayers [163]. They carried out the experiments in gel... 

Figure 7.22b is a similar plot for the other two lipids considered olive oil (unfilled symbols) and octanol (filled symbols). Both lipids can be described by a bilinear relationship, patterned after the case in Fig. 7.19d [Eq. (7.44)]. Octanol shows a declining log Pe relationship for very lipophilic molecules (log Kd > 2). The probe set of 32 molecules does not have examples of very hydrophilic molecules, with log Kd < —2, so the expected hydrophilic ascending part of the solid curve in Fig. 7.22b is not fully shown. Nevertheless, the shape of the plot is very similar to that reported by Camenisch et al. [546], shown in Fig. 7.8c. The UWL in the latter study (stirred solutions) is estimated to be 460 pm (Fig. 7.8b), whereas the corresponding value in unstirred 96-well microtiter late assay is about 2300 pm. For this reason, the high point in Fig. 7.22b is 16 x 10-6 cm/s, whereas it is 70 x 10 6 cm/s in Fig. 7.8c.

Fig. 6.10 Methods of preparation of bilayer lipid membranes. (A) A Teflon septum with a window of approximately 1mm2 area divides the solution into two compartments (a). A drop of a lipid-hexane solution is placed on the window (b). By capillary forces the lipid layer is thinned and a bilayer (black in appearance) is formed (c) (P. Mueller, D. O. Rudin, H. Ti Tien and W. D. Wescot). (B) The septum with a window is being immersed into the solution with a lipid monolayer on its surface (a). After immersion of the whole window a bilayer lipid membrane is formed (b) (M. Montal and P. Mueller). (C) A drop of lipid-hexane solution is placed at the orifice of a glass capillary (a). By slight sucking a bubble-formed BLM is shaped (b) (U. Wilmsen, C. Methfessel, W. Hanke and G. Boheim)...

In addition, the physical dimensions of the cells making up the monolayer should be considered. Cell shape can influence the relative contributions of the paracellular and transcellular pathways. For example, junctional density is greater in cells that are narrow or of small diameter than in cells that are wide or spread out on the substrate. The height of the cells can impact the path length traveled by a permeant, as will the morphology of the junctional complex and lateral space (Section m.B.2). It is unknown how the mass of lipid or membrane within a cell influences transcellular flux of a lipophilic permeant. 

Recently McConnell has introduced the technique of labelling proteins lipid membranes, and DNA, with a stable organic free radical, the nitro-xide radical, see reference (24). A measurement of the line shapes of the ESR signal of this label has revealed the rotational times of the molecules to which it is bound. If paramagnetic analogues of the anti-tumour compounds are found then their progress within a cell will be readily followed using ESR. Complexes of all the metals of Table 1 with odd numbers of electrons (d1, d3, d5 and d1) are potentially useful. Thus... 

Hydrophobic interactions, on the other hand, are strong, indifferent to local details, and are relatively long range. If transient direct or water-separated contacts occur between nonpolar side chains, the net effect could be local organization and an overall compaction of the polypeptide chain. Whereas the strengths of hydrophobic interactions must be considerably reduced in 8 M urea, they clearly are not eliminated, as evidenced by the persistence of lipid bicelles. Thus hydrophobic interactions probably play some role in persistent global structure, the importance of which can be tested by replacing multiple hydrophobic side chains with similarly shaped polar ones. 

Concerning the nature and structure of such amyloid peptide or protein channels, oligomers with annular morphologies have in fact been observed by EM for a-synuclein (Lashuel et al., 2002) and equine lysozyme (Malisauskas et al., 2003) even in the absence of any lipids or membranes. Channel-like structures have also been reconstituted in liposomes and observed by SFM for A/ i 4o, A/ j 42, human amylin, a-synuclein, ABri, ADan, and serum amyloid A (Fig. 5A Lin et al., 2001 Quist et al., 2005). Doughnut-shaped structures with a diameter of 10-12 nm and a central hole size of 1-2 nm (Fig. 5B) were imaged on top of lipid membranes (Quist et al., 2005). However, the radius of curvature of the SFM tips meant that it is not possible to say whether the pores were really traversing the lipid bilayer. 

Figure 3 (Plate 2). Representation of molecular structure in MD simulations. Shown here is the SOPC lipid, discussed in the text. The numbers at each atom indicate the partial charge on the atom. The space-filling picture on the left gives insight into the van der Waals radii of the various groups, and thus into the shape of the molecule. Reproduced from (58) with permission from the Biophysical Society...

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