Cell membrane polar molecules

Drug molecules are transported across cell membranes. Because of the lipid bilayer construction of the membrane (Appendix 2), nonpolar (lipid-soluble) molecules are able to diffuse and penetrate the cell membrane. Polar molecules, however, cannot penetrate the cell membrane readily via passive diffusion and rely on other transport mechanisms. 

Figure 20-2 Phospholipids are substituted esters essential to the structures of cell membranes. These molecules aggregate to form (A) a micelle or (B) a lipid bilayer. The polar head groups and nonpolar tails in phospholipids drive these aggregations. (After Biochemistry, 6th ed., by Jeremy M. Berg, John L. Tymoczko, and Lubert Stryer. W. H. Freeman and Company. Copyright 1975, 1981, 1988, 1995,...

The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules (Figure 25-1). These are oriented so that their polar groups face outward to the aqueous medium, as in the cell membrane (Chapter 14). The protein moiety of a lipoprotein is known as an apo-lipoprotein or apoprotein, constituting nearly 70% of some HDL and as litde as 1% of chylomicrons. Some apolipoproteins are integral and cannot be removed, whereas others are free to transfer to other hpoproteins. 

Taste-modality recognition is a function of the cells of the taste buds. Perception of the sensation is a result of complex processes in the brain. The biological events that are discussed are those that occur, or are suggested as occurring, in taste-receptor cells, beginning at the instant when the taste-stimulus molecule interacts with the cell, until the membrane of the receptor cell is polarized. These are peripheral events. However, our knowledge of the peripheral mechanisms in taste perception is not sufficiently complete to provide a detailed, biophysical explanation of this phenomenon. Nevertheless, several stages in this explanation have been hypothesized, and some are demonstrable. 

While many biological molecules may be targets for oxidant stress and free radicals, it is clear that the cell membrane and its associated proteins may be particularly vulnerable. The ability of the cell to control its intracellular ionic environment as well as its ability to maintain a polarized membrane potential and electrical excitability depends on the activity of ion-translocating proteins such as channels, pumps and exchangers. Either direct or indirect disturbances of the activity of these ion translocators must ultimately underlie reperfiision and oxidant stress-induced arrhythmias in the heart. A number of studies have therefore investigated the effects of free radicals and oxidant stress on cellular electrophysiology and the activity of key membrane-bound ion translocating proteins. 

Fig. 7 Diagrammatic representation of the fluid mosaic model of the cell membrane. The basic structure of the membrane is that of a lipid bilayer in which the lipid portion (long tails) points inward and the polar portion (round head ) points outward. The membrane is penenetrated by transmembrane (or integral) proteins. Attached to the surface of the membrane are peripheral proteins (inner surface) and carbohydrates that bind to lipid and protein molecules (outer surface). (Modified from Ref. 14.)...

While both paracellular and passive transcellular pathways are available to a solute, the relative contribution of each to the observed transport will depend on the properties of the solute and the membrane in question. Generally, polar membrane-impermeant molecules diffuse through the paracellular route, which is dominated by tight junctions (Section III.A). Exceptions include molecules that are actively transported across one or both membrane domains of a polarized cell (Fig. 2). The tight junction provides a rate-limiting barrier for many ions, small molecules, and macromolecules depending on the shape, size, and charge of the solute and the selectivity and dimensions of the pathway. 

The lipid bilayer arrangement of the plasma membrane renders it selectively permeable. Uncharged or nonpolar molecules, such as oxygen, carbon dioxide, and fatty acids, are lipid soluble and may permeate through the membrane quite readily. Charged or polar molecules, such as glucose, proteins, and ions, are water soluble and impermeable, unable to cross the membrane unassisted. These substances require protein channels or carrier molecules to enter or leave the cell. 

In the process of mediated transport, carrier proteins embedded within the plasma membrane assist in the transport of larger polar molecules into or out of the cell. When a given substance attaches to a specific binding site on the carrier protein, the protein undergoes a conformational change such that this site with the bound substance moves from one side of the plasma membrane to the other. The substance is then released. Mediated transport displays three important characteristics influencing its function ... 

The cells of all contemporary living organisms are surrounded by cell membranes, which normally consist of a phospholipid bilayer, consisting of two layers of lipid molecules, into which various amounts of proteins are incorporated. The basis for the formation of mono- or bilayers is the physicochemical character of the molecules involved these are amphipathic (bifunctional) molecules, i.e., molecules which have both a polar and also a non-polar group of atoms. Examples are the amino acid phenylalanine (a) or the phospholipid phosphatidylcholine (b), which is important in membrane formation. In each case, the polar group leads to hydrophilic, and the non-polar group to hydrophobic character. 

To reach such a site, a molecule must permeate through many road blocks formed by cell membranes. These are composed of phospholipid bilayers - oily barriers that greatly attenuate the passage of charged or highly polar molecules. Often, cultured cells, such as Caco-2 or Madin-Darby canine kidney (MDCK) cells [1-4], are used for this purpose, but the tests are costly. Other types of permeability measurements based on artificial membranes have been considered, the aim being to improve efficiency and lowering costs. One such approach, PAMPA, has been described by Kansy et al. [5],... 

Amphipathic molecules can form bilayered lamellar structures spontaneously if they have an appropriate geometry. Most of the major cell membrane lipids have a polar head, most commonly a glycerophosphorylester moiety, and a hydrocarbon tail, usually consisting of two... 

Figure 6.11. Intracellular Ca2+ levels during neutrophil activation with fMet-Leu-Phe. Neutrophil suspensions were loaded with Fluo-3 AM for 15 min. This molecule is membrane permeable but cleaved by intracellular esterase activity to yield the polar molecule Fluo-3, which is thus trapped within the cell. The neutrophils were then suspended in buffer that was devoid of Ca2+, and treated as shown. In (a), 1 mM Ca2+ and 1 /tM fMet-Leu-Phe were added to the suspension, as indicated by the arrows. In (b), 1 mM EGTA and 1 pM fMet-Leu-Phe were added as shown. Thus, in (a), the change in intracellular Ca2+ is due to mobilisation of intracellular Ca2+ stores and the influx of extracellular Ca2+, whereas in (b), the Ca2+ rise is due solely to release of Ca2+ from intracellular stores.

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