Cell membrane, barrier

Additional cell membrane barriers (plasma membrane, and possibly organelle membranes) will have to be overcome if the drug target is located intracellularly. It thus turns out... 

Facilitated diffusion Large molecules (e. g. glucose, protein, organic ions) cannot diffuse across the cell membrane barrier unaided. Mechanisms in the form of channels or transport proteins (= carriers) are therefore required to enable molecules to penetrate the impermeable... 

Simkiss, K.. Ecotoxicants at the cell membrane barrier. In Ecotoxicology A Hierarchical Treatment, edited by M. Newman and C.H. Jagoe, Boca Raton, FL, Lewis Publishers, pp. 59-83, 1995. 

The equation in this form cannot be used directly since we do not have experimental values for the partition coefficient of the permeability barrier within the membrane. What we do have for each permeant are values of partition coefficients for various model organic solvents which we want to test as descriptors of the cell membrane barrier, and hence as possible estimates of the K values. In order to test the reasonableness of a particular choice of organic solvent we transform Eqn. 8 into the generalised form... 

There are different techniques to overcome the cell membrane barrier and introduce exogenous impermeable compounds, such as dyes, DNA, proteins, and amino acids into the ceU. Some of the methods include lipofection, fusion of cationic liposome, electroporation, microinjection, optoporation, electroinjection, and biolistics. Electroporation has the advantage of being a noncontact method for transient permeabilization of cells (Olofsson et al., 2003). In contrast to microinjection techniques for single cells and single nuclei (Capecchi, 1980), the electroporation technique can be applied to biological containers of sub-femtoliter volumes, that are less than a few micrometers in diameter. Also, it can be extremely fast and well-timed (Kinosita et al., 1988 Hibino et al., 1991), which is of importance in studying fast-reaction phenomena (Ryttsen et aL, 2000). 

Due to their small size, NPs can efficiently penetrate across the cell membrane barrier to increase the efficiency of gene delivery. 

Although the active transport of riboflavin across the gut wall and across other cell membrane barriers within the animal is a saturable process, if large pharmacological amounts are present then the slower and less efficient but nonsaturable process of passive absorption predominates and contributes significantly to the total mass transfer. The active transport process is increased in riboflavin deficiency and decreased if the riboflavin content of the tissues is high. The transport pathway involves calcium and calmodulin but not sodium. Specific riboflavin receptors have recently been identified, as has a role for microtubules in transport. 

Nanospheres as a drug delivery system could provide many advantages. Since nanospheres are submicron in size, they could be taken up more efficiently by the cells than the larger size particles. Furthermore, nanospheres could cross the cell membrane barriers by transcytosis. Drug molecules such as proteins and peptides and also DNA, which have a larger... 

Phosphatidylcholine is an important component of cell membranes but cell mem branes are more than simply lipid bilayers Although their composition varies with their source a typical membrane contains about equal amounts of lipid and protein and the amount of cholesterol m the lipid fraction can approximate that of phosphatidylcholine The lipid fraction is responsible for the structure of the membrane Phosphatidyl choline provides the bilayer that is the barrier between what is inside the cell and what IS outside Cholesterol intermingles with the phosphatidylcholine to confer an extra measure of rigidity to the membrane... 

Cell membranes are lipophilic and designed to be barriers against large anionic molecules, although there is a natural mechanism for intercellular transport of anionic oligonucleotides. In order to enhance membrane transport, antisense oligonucleotides are frequentiy modified by covalent attachment of carrier molecules or lipophilic groups. 

Cell membrane The cell membrane is composed of about 45% lipid and 55% protein. The lipids form a bilayer that is a continuous nonpolar hydrophobic phase in which the proteins are embedded. The cell membrane is a highly selective permeability barrier that controls the entry of most substances into the cell. Important enzymes in the generation of cellular energy are located in the membrane. 

With the adequacy of lipid bilayer membranes as models for the basic structural motif and hence for the ion transport barrier of biological membranes, studies of channel and carrier ion transport mechanisms across such membranes become of central relevance to transport across cell membranes. The fundamental principles derived from these studies, however, have generality beyond the specific model systems. As noted above and as will be treated below, it is found that selective transport... 

Phospholipids are found widely in both plant and animal tissues and make up approximately 50% to 60% of cell membranes. Because they are like soaps in having a long, nonpolar hydrocarbon tail bound to a polar ionic head, phospholipids in the cell membrane organize into a lipid bilayer about 5.0 nm (50 A) thick. As shown in Figure 27.2, the nonpolar tails aggregate in the center of the bilayer in much the same way that soap tails aggregate in the center of a micelle. This bilayer serves as an effective barrier to the passage of water, ions, and other components into and out of cells. 

However, there are disadvantages to using immobilised cells. The cell may contain numerous catalytically active enzymes, which may catalyse unwanted side reactions. Also, the cell membrane itself may serve as a diffusion barrier, and may reduce productivity. The matrix may sharply reduce productivity if the microorganism is sensitive to product inhibition. One of the disadvantages of immobilised cell reactors is that the physiological state of the microorganism cannot be controlled. 

The size of plasmids used for transfection can vary considerably, but most plasmids are 4,000 to 10,000 base pairs in size. Despite their differences all plasmids face the same barriers when transfected. Transfected DNA has to cross the cell membrane or the endosomal membrane, it has to be transported into the nucleus, and it has to be protected against cellular nucleases and degradation... 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

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