The Cell Plasma Membrane

Most of the early work on membranes was based on experiments with erythrocytes. These cells were first described by Swammerdam in 1658 with a more detailed account being given by van Leeuwenhoek (1673). The existence of a cell (plasma) membrane with properties distinct from those of protoplasm followed from the work of Hamburger (1898) who showed that when placed in an isotonic solution of sodium chloride, erythrocytes behaved as osmometers with a semipermeable membrane. Hemolysis became a convenient indication of the penetration of solutes and water into the cell. From 1900 until the early 1960s studies on cell membranes fell into two main categories increasingly sophisticated kinetic analyses of solute translocation, and rather less satisfactory examinations of membrane composition and organization. 

Gryns (1896), Hedin (1897), and especially Overton (1900) looked at the permeability of a wide range of different compounds, particularly non-electrolytes, and showed that rates of penetration of solutes into erythrocytes increased with their lipid solubility. Overton correlated the rate of penetration of the solute with its partition coefficient between water and olive oil, which he took as a model for membrane composition. Some water-soluble molecules, particularly urea, entered erythrocytes faster than could be attributed to their lipid solubility—observations leading to the concept of pores, or discontinuities in the membrane which allowed water-soluble molecules to penetrate. The need to postulate the existence of pores offered the first hint of a mosaic structure for the membrane. Jacobs (1932) and Huber and Orskov (1933) put results from the early permeability studies onto a quantitative basis and concluded molecular size was a factor in the rate of solute translocation. 

From 1938 until the early 1960s Wilbrandt undertook extensive experiments on glucose uptake into erythrocytes. It was appreciated 

Major developments in transport kinetics followed from the work of Gardos who, in 1954, succeeded in restoring K+ uptake in red cell ghosts if ATP was added to the medium. Hoffman (1962) showed that in the presence of inosine, the ghosts extruded Na+. Three components of efflux were distinguished active transport, passive transport, and 

The experiments were continued by Hoffman and Whittam, who concluded that a protein, an ATPase, in the membrane was necessary for active transport and was vectorially organized, with ATP and Na+ being required internally and K+ externally where ouabain was inhibitory. The ATPase was finally identified as the sodium pump by Skou (1957) it vectorially translocated Na+ and K+ across the membrane, and was phosphorylated transiently in the process. 

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To reach the reductive step of the azo bond cleavage, due to the reaction between reduced electron carriers (flavins or hydroquinones) and azo dyes, either the reduced electron carrier or the azo compound should pass the cell plasma membrane barrier. Highly polar azo dyes, such as sulfonated compounds, cannot pass the plasma membrane barrier, as sulfonic acid substitution of the azo dye structure apparently blocks effective dye permeation [28], The removal of the block to the dye permeation by treatment with toluene of Bacillus cereus cells induced a significant increase of the uptake of sulfonated azo dyes and of their reduction rate [29]. Moreover, cell extracts usually show to be more active in anaerobic reduction of azo dyes than whole cells. Therefore, intracellular reductases activities are not the best way to reach sulfonated azo dyes reduction the biological systems in which the transport of redox mediators or of azo dye through the plasma membrane is not required are preferable to achieve their degradation [13]. 

The biosynthetic, secretory pathway is responsible for protein sorting and delivery and allows, among other functions, for cell-cell communication through secreted products. This delivery process starts at the endoplasmic reticulum (ER), to finish in the cell plasma membrane or, in some cases, in specific intracellular organelles. To accomplish this, specific proteins must be properly directed to the correct destination, while other proteins are retained as residents within specific organelles along the way. 

The cell plasma membrane separates the cell cytoplasm from the external medium. The composition of the cytoplasm must be tightly controlled to optimize cellular processes, but the composition of the external medium is highly variable. The membrane is hydrophobic and impedes solute diffusion. But it also facilitates and regulates solute transfers as the cell absorbs nutrients, expels wastes and maintains turgour. 

Zhang, P., Johnson, P. S., Zollner, C., et al. (1999) Mutation of human mu opioid receptor extracellular disulfide cysteine residues alters hgand binding but does not prevent receptor targeting to the cell plasma membrane. Brain Res. Mol. Brain Res. 72, 195-204. 

Another key group of transporters present in the cell plasma membrane is integrated by Na +, K +, and Ca2 + channels. Among them, there are... 

INTERACTIONS BETWEEN LAMELLAR AND INVERTED HEXAGONAL Hn PHASE OF CL/DNA COMPLEXES AND ANIONIC GIANT LIPOSOMES MIMICKING THE CELL PLASMA MEMBRANE... 

Finally, binding studies revealed the existence, at the level of the cell plasma membrane, of specific polyphenol binding sites in the rat brain. Structure-activity data support the hypothesis that these specific binding sites may mediate numerous biological effects of these polyphenols, including their neuroprotective abilities. 

Lipoplexes and polyplexes are DNA-cationic molecular complexes, formed, respectively, by DNA interaction with lipids or polymers. The main property of these complexes is to allow easier passage of DNA through the cell plasma membrane, by means of two mechanisms DNA charge neutralization and plasmid condensation, which reduces its size. Such complexes are formed by an excess of positive charges to neutralize DNA phosphate groups, resulting in transfecting particles with a net... 

FIGURE 4.3 High magnification transmission electron micrographs of multilamellar membrane structures in the intercellular space of the cornified part of human epidermis. (A) cryo-electron micrograph of vitreous section. (B, C) conventional electron micrographs of resin embedded sections. The cell plasma membranes appear as 3.8 nm wide bilayers in (A) (open white arrow). A 16 nm broad zone of electron dense material, the cornified cell envelope (white asterix), is directly apposed to the cytoplasmic side of the bilayer plasma membranes in the native sample (A) (open white arrow). Scale bar 50 nm (A). Scale bars 25 nm (B, C) adapted from measures given in Swartzendruber et al. (1989). (A) reprinted from Norlen (2003). With permission from Blackwell Science Publications. (B, C) reprinted from Swartzendruber et al. (1989). With permission from Blackwell Science Publications. 

Revealing the dynamic organization of the cell plasma membrane at the submicrcHi level is a challenging task. On one hand, electron microscopy resolves nanometric features, and yet it cannot be easily applied to live cells under physiological conditions. On the other hand, standard optical microscopy unravels details of live cell membranes, but is limited to a resolution of about 200 nm. 

The cell plasma membrane consists of a variety of proteins associated with the lipid bilayer and they perform multitasks in cell function. The control of transport of ions and molecules across membrane is accomplished through specialized function of membrane proteins. These proteins are distributed in membrane on the outer surface, some on the inner surface, and some others are transmembrane proteins with external and cytoplasmic domains. The majority of the transmembrane proteins are the ion channels or signaling proteins. Generally, hpid to protein ratio is 60 40 but this ratio is found variable in different cells and types of membranes. Membrane proteins impart the dynamic structure and selectivity to membrane function. Both proteins and hpids show motional and diffusion properties within the bUayer structure. 

The liposome can be made in such a way that they mimic the cellular plasma membrane and drugs/other potential impairment molecules can be loaded in the aqueous core or bUayer milieu of the liposome. Generally, the liposomal membrane fuses with the cell plasma membrane and releases the contents into the cytosol. Thus, liposomes provide an effective tool for overcoming the bUayer barrier and dehver dmgs to targets in cells. 

The cell (plasma) membrane is a fluid mosaic of lipids and proteins. 

The location of transporters at the cell plasma membrane is a critical issue because most of the cells involved in the A, D, E pharmacokinetic processes are polarized. Hence then-apical (luminal) and basolateral (abluminal) membranes do not have the same populations of transporters (Eigure 34.4). The same transporter is rarely found at both the apical and basolateral membranes. But most of the ABC and SLC transporters are located at either the apical or the basolateral epithelial membranes, and their location helps to define the direction of substrate transport and the resulting pharmacokinetic event. 

Fig. 4 Mitochondrial permeability transition (MPT) can cause either severe ATP depletion and cell necrosis, or caspase activation and apoptosis, (a) Opening of the MPT pore allows a reentry of protons through the pore, thus bypassing ATP synthase and preventing mitochondrial ATP generation. MPT also causes an influx of water driven by the oncotic pressure of matrix proteins. The outer membrane ruptures from matrix swelling, (b) When MPT only occurs in some mitochondria, the unaffected organelles synthesize enough ATP to prevent necrosis, while the affected mitochondria release cytochrome c, which activates caspases to trigger apoptosis. However, when MPT occurs in all mitochondria, severe ATP depletion causes cell swelling, rupture of the cell plasma membrane and necrosis...

Porosome, a supramolecular structure at the cell plasma membrane acting as the universal secretory machinery in cells. Membrane-bound secretory vesicles dock at the porosome and fuse to release their content [L. L. Anderson, J. Cell. Mol. Med. 2006, 10, 126],... 

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