Lipid Bilayer Concept

The history of the development of the bilayer membrane model is fascinating, and spans at least 300 years, beginning with studies of soap bubbles and oil layers on water [517-519]. 

In 1672 Robert Hooke observed under a microscope the growth of black spots on soap bubbles [520]. Three years later Isaac Newton [521], studying the images 

Ben Franklin, a self-trained scientist of eclectic interests, but better known for his role in American political history, was visiting England in the early 1770s. He published in the Philosophical Transactions of the Royal Society in 1774 [552]  

Franklin mentioned Pliny s account of fisherman pouring oil on troubled waters in ancient times, a practice that survives to the present. (Franklin s experiment was reenacted by the author at the pond on Clapham Common with a teaspoon of olive oil. The spreading oil covered a surface not larger than that of a beach towel-it appears that technique and/or choice of oil is important. The olive oil quickly spread out in circular patterns of brilliant prismatic colors, but then dissolved from sight. Indeed, the pond itself has shrunken considerably over the intervening 230 years.) 

Franklin s teaspoon of oil (assuming a density 0.9 g/mL and average fatty-acid molecular weight 280 g/mol) would contain 10+22 fatty-acid tails. The half-acre pond surface covered by the oil, 2000 m2, is about 2 x 10+23 A2. So, each tail would be expected to occupy about 20 A2, assuming that a single monolayer (25 A calculated thickness) of oil formed on the surface of the pond. 

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Tien, T. H. Ottova, A. L., The lipid bilayer concept and its experimental realization From soap bubbles, kitchen sink, to bilayer lipid membranes, J. Membr. Sci. 189,83-117 (2001). 

In addition to the self-spreading lipid bilayer, it was also found that a lipid mono-layer showed similar spreading behavior on a hydrophobic surface (Figure 13.6) [51]. By fabricating an appropriate hydrophobic surface pattern, the spreading area and direction can be easily controlled. For both the self-spreading bilayer and monolayer, non-biased molecular transportation is an important key concept for the next generation of microfiuidic devices. 

The most intriguing aspect of the self-spreading lipid bilayer is that any molecule in the bilayer can be transported without any external bias. The unique characteristic of the spreading layer offers the chance to manipulate molecules without applying any external biases. This concept leads to a completely non-biased molecular manipulation system in a microfluidic device. For this purpose, the use of nano-space, which occasionally offers the possibility of controlling molecular diffusion dynamics, would be a promising approach. 

Here the basic concepts and the method for strictly determining DD sites in lipid bilayer membranes are viewed, together with some examples of their applications. 

Basic concepts and the methods for determining DD sites in lipid bilayer membranes have been developed by NMR on the atomic site level. Lipid bilayer interfaces as delivery sites can be specified by taking advantage of the site selectivity of NMR. DD sites can be generally classified into the three categories in Fig. 6. The distinction is based on the difference in the micropolarity in membranes around the drug. It has been briefly mentioned how to evaluate dynamic properties of drugs in membranes. 

Our knowledge of biological membrane ultrastructure has increased considerably over the years as a result of rapid advances in instrumentation. Although there is still controversy over the most correct biological membrane model, the concept of membrane structure presented by Davson and Danielli of a lipid bilayer is perhaps the one best accepted [12,13]. The most current version of that basic model, illustrated in Fig. 7, is referred to as the fluid mosaic model of membrane structure. This model is consistent with what we have learned about the existence of specific ion channels and receptors within and along surface membranes. 

Gorter and Grendel in 1925 [527], drawing on the work of Langmuir, extracted lipids from RBC ghosts and formed monolayers. They discovered that the area of the monolayer was twice that of the calculated membrane surface of intact RBC, indicating the presence of a bilayer. This was the birth of the concept of a lipid bilayer as the fundamental structure of cell membranes (Fig. 7.1). 

Myelin in situ has a water content of about 40%. The dry mass of both CNS and PNS myelin is characterized by a high proportion of lipid (70-85%) and, consequently, a low proportion of protein (15-30%). By comparison, most biological membranes have a higher ratio of proteins to lipids. The currently accepted view of membrane structure is that of a lipid bilayer with integral membrane proteins embedded in the bilayer and other extrinsic proteins attached to one surface or the other by weaker linkages. Proteins and lipids are asymmetrically distributed in this bilayer, with only partial asymmetry of the lipids. The proposed molecular architecture of the layered membranes of compact myelin fits such a concept (Fig. 4-11). Models of compact myelin are based on data from electron microscopy, immunostaining, X-ray diffraction, surface probes studies, structural abnormalities in mutant mice, correlations between structure and composition in various species, and predictions of protein structure from sequencing information [4]. 

This review obviously reflects the preferences of the author in stressing the application of FT - IR to amphiphile phase behavior and the kinetics of interfacial phenomena. In some sense, FT - IR may be considered an emerging technique in studies of the phase behavior of surfactants. However, from the wide range of studies of lipid bilayers mentioned, it seems that the concept of using FT - IR to probe surfactant molecule associative properties in other aggregates such as micelles, gels and vesicles can be considered a logical extension. 

Note, however that the concepts about the lipid membrane as the isotropic, structureless medium are oversimplified. It is well known [19, 190] that the rates and character of the molecular motion in the lateral direction and across the membrane are quite different. This is true for both the molecules inserted in the lipid bilayer and the lipid molecules themselves. Thus, for example, while it still seems possible to characterize the lateral movement of the egg lecithin molecule by the diffusion coefficient D its movement across the membrane seems to be better described by the so-called flip-flop mechanism when two lipid molecules from the inner and outer membrane monolayers of the vesicle synchronously change locations with each other [19]. The value of D, = 1.8 x 10 8 cm2 s 1 [191] corresponds to the time of the lateral diffusion jump of lecithin molecule, Le. about 10 7s. The characteristic time of flip-flop under the same conditions is much longer (about 6.5 hours) [19]. The molecules without long hydrocarbon chains migrate much more rapidly. For example for pyrene D, = 1.4x 10 7 cm2 s1 [192]. 

Perhaps the most important step in the development of our current understanding of biomembranes was the introduction of the fluid mosaic model [28] (Figure 1.4) [40]. This model describes the cell membrane as a fluid two-dimensional lipid bilayer matrix of about 50 A thickness with its associated proteins. It allows for the lateral diffusion of both lipids and proteins in the plane of the membrane [41] but contains little structural detail. This model has been further developed and it has been assumed that the membrane consists of solid domains coexisting with areas of fluid-disordered membrane lipids that may also contain proteins [42]. This concept has... 

In 1925 Evert Gorter and F. Grendel estimated that the lipids from erythrocytes (red blood cells), when spread as a monomolecular layer, cover an area nearly twice the surface area of the cells. The amount of lipid present is apparently sufficient to form a double layer in the membrane. Moreover, the penetration of a series of substances across membranes often depends on the relative lipid solubility of the molecules. This circumstantial evidence led to the concept of a biological membrane composed primarily of a lipid bilayer. 

On the basis of the dynamic properties of proteins in membranes, S. Jonathan Singer and Garth Nicolson proposed the concept of a fluid mosaic model for the overall organization of biological membranes in 1972 (Figure 1230). The essence of their model is that membranes are two-dimensional solutions of oriented lipids and globular proteins. The lipid bilayer has a dual role it is both a solvent for integral membrane proteins and a permeability barrier. Membrane proteins are free to diffuse laterally in the lipid matrix unless restricted by special interactions. 

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