Membrane fluid phase

Figure 41 -15. Two types of endocytosis. An endocytotic vesicle (V) forms as a result of invagination of a portion of the plasma membrane. Fluid-phase endocytosis (A) is random and nondirected. Receptor-mediated endocytosis (B) is selective and occurs in coated pits (CP) lined with the protein clathrin (the fuzzy material). Targeting is provided by receptors (black symbols) specific for a variety of molecules. This results in the formation of a coated vesicle (CV).

If Henry s law applies, the concentrations in fluid phases and the membrane are related by ... 

S. Murad, R. Madhusudan, J. G. Powles. A molecular simulation to investigate the possibility of electro-osmosis in non-ionic solutions with uniform electric fields. Mol Phys 90 671, 1997 R. Madhususan, J. Lin, S. Murad. Molecular simulations of electro-osmosis in fluid mixtures using semi-permeable membranes. Eluid Phase Equil 150 91, 1998. 

Most methods of separating molecules in solution use direct contact of immiscible fluids or a sohd and a fluid. These methods are helped by dispersion of one phase in the other, fluid phase, but they are hindered by the necessity for separating the dispersed phase. Fixed-bed adsorption processes overcome the hindrance by immobilizing the solid adsorbent, but at the cost of cyclic batch operation. Membrane processes trade direct contact for permanent separation of the two phases and offer possibilities for high selectivity. 

Bone is a porous tissue composite material containing a fluid phase, a calcified bone mineral, hydroxyapatite (HA), and organic components (mainly, collagen type). The variety of cellular and noncellular components consist of approximately 69% organic and 22% inorganic material and 9% water. The principal constiments of bone tissue are calcium (Ca ), phosphate (PO ), and hydroxyl (OH ) ions and calcium carbonate. There are smaller quantities of sodium, magnesium, and fluoride. The major compound, HA, has the formula Caio(P04)g(OH)2 in its unit cell. The porosity of bone includes membrane-lined capillary blood vessels, which function to transport nutrients and ions in bone, canaliculi, and the lacunae occupied in vivo by bone cells (osteoblasts), and the micropores present in the matrix. 

The fluidity is one of the most vital properties of biological membranes. It relates to many functions involved in biological system, and effective biomembrane mimetic chemistry depends on the combination of both stability and mobility of the model membranes. However, in the polymerized vesicles the polymer chain interferes with the motion of the side groups and usually causes a decrease or even the loss of the fluid phases inside the polymerized vesicle (72,13). 

In another approach, the isotropic hyperflne coupling constant (A0 in Figure 10.2) of 16-SASL or 16-PC can be measured for fluid-phase membranes. A decrease in the A0 value indicates an increase in hydrophobicity at the 16-SASL position (Figure 10.5c). However, this constant reflects only the hydrophobicity of the membrane center. 

Kusumi, A., W. K. Subczynski, M. Pasenkiewicz-Gierula, J. S. Hyde, and H. Merkle. 1986. Spin-label studies on phosphatidylcholine-cholesterol membranes Effects of alkyl chain length and unsaturation in the fluid phase. Biochim. Biophys. Acta 854 307-317. 

Attempts to study the entry of ES products into cells using markers of fluid phase endocytosis yielded unexpected results. When larvae browse resistant IEC-6 cells in the presence of extracellular fluorescent dextran, dextran enters the cytoplasm of a significant proportion of the cells in the mono-layer (Butcher et al., 2000). The parameters of dextran entry are most compatible with the conclusion that larvae wound the plasma membranes of IEC-6 cells that is, they create transient breaches in the membrane that allow impermeant markers to enter the cell (McNeil and Ito, 1989). Wounding is considered to be a common occurrence in intestinal epithelia (McNeil and Ito, 1989). Injured cells are able to heal their wounds by recruiting vesicles to seal the breach (Steinhardt et al., 1994). In an experimental system, healing allows the injured cell to retain cytoplasmic dextran. In epithelial cell cultures inoculated with T. spiralis larvae, the relationship between glycoprotein delivery and injury of plasma membranes is not clear, i.e. dextran-laden cells do not always stain with Tyv-specific antibodies and... 

To discuss the models in this section, we should mention two issues. First, the models assume the membrane is sufficiently soft that the tilt direction can vary with an energy cost that scales as (Vc(j)2. This is appropriate if the membrane is in a fluid phase like a smectic-C liquid crystal, with order in the tilt direction but not in the positions of the molecules. It is also appropriate if the membrane is in a tilted hexatic phase, with order in the orientations of the intermolecular bonds as well as the tilt. However, this assumption is not appropriate if the membrane is in a crystalline phase, because the tilt direction would be locked to the crystalline axes, and varying it would cost more energy than (V(f>)2. 

Chiu, S. W., Clark, M., Balaji, V., Subramaniam, S., Scott, H. L. and Jakobsson, E. (1995). Incorporation of surface tension into molecular dynamics simulation of an interface a fluid phase lipid bilayer membrane, Biophys. J., 69,1230-1245. 

The cellular uptake of AS-ODN is an energy-dependent process and takes place in a saturable and sequence-independent manner [120,121]. The exact mechanism of uptake remains controversial. From in vitro experiments, some authors have proposed that the uptake is endocytic and mediated by membrane receptor proteins. The receptor responsible for the cellular uptake of AS-ODNs was reported to consist of both a 30-kDa protein [122] and an 80-kDa membrane protein [121]. However, other workers have argued that AS-ODN binding to membrane proteins is relatively non-specific and is mostly charge associated, consistent with adsorptive endocytosis or fluid-phase pinocytosis [101]. As a result of these conflicting reports, it is unlikely that in vitro data can be safely extrapolated to what occurs in the intact organism. 

Diffusion (A). Lipophilic substances (red dots) may enter the membrane from the extracellular space (area shown in ochre), accumulate in the membrane, and exit into the cytosol (blue area). Direction and speed of permeation depend on the relative concentrations in the fluid phases and the membrane. The steeper the gradient (concentration difference), the more drug will be diffusing per unit of time (Pick s Law). The lipid membrane represents an almost insurmountable obstacle for hydrophilic substances (blue triangles). 

Endocytosis involves the ceUular uptake of exogenous molecules or complexes inside plasma membrane-derived vesicles. This process can be divided into two major categories (1) adsorptive or phagocytic uptake of particles that have been bound to the membrane surface and (2) fluid or pinocytotic uptake, in which the particle enters the cell as part of the fluid phase. The solute within the vesicle is released intracellularly, possibly through lysosomal digestion of the vesicle membrane or by intermembrane fusion (Fig. 3.4). 

Fig. I. Endocytic pathways used by cells to internalize soluble macromolecules [25] fluid-phase pinocytosis (1), adsorptive pinocytosis (2), and receptor-mediated endocytosis (pinocytosis) (6). Each of these processes involves a formation of a sealed vesicle formed from the plasma membrane which encloses part of the extracellular medium. The internalization of a polymer-drug conjugate (P-D), and targeted polymer-drug conjugate ( => —P-D) is shown. Other abbreviations — = cell surface receptor/antigen 1 = clathrin molecule X = lysosomal enzyme. Fluid-phase pinocytosis (1) and adsorptive pinocytosis (2) are nonspecific processes which direct the macromolecule into the lysosomal compartment of the cell. Once P-D is internalized, whether by (1) or (2), the resulting endosome (3) is ultimately fused with a primary lysosome (4) forming a secondary lysosome (5). In the latter compartment P-D is in contact with several types of lysosomal enzymes. The membrane of (5) is impermeable to macromolecules. Consequently, the structure of P-D may be designed in such...

Let us assume some small number n of lipid molecules can form a relatively stable solid phase cluster when the temperature and composition of the lipid mixture is such that, according to the phase diagram, solid phase can exist in equilibrium with the fluid phase. (For example, we later assume that n 10.) Let us further assume that (1) the temperature and composition of the lipid mixture is such that X is small, X 1, and (2) all the solid phase present is in the form of clusters of n molecules each. If the clusters are randomly distributed in the plane of the membrane, then each cluster will be surrounded by a number of fluid molecules of the order of magnitude of N n/X. The area occupied by the surrounding fluid phase molecules is then NA0 where, A0 60A2. Let us now calculate lower limit on X, Xmin, such that each molecule in... 

The 13C nuclear resonance studies in my report provide some informations on lipid membrane fluctuations in binary mixtures. Totally unsolved problems include an appropriate two-dimensional Debye-Huckel theory for membranes, and theoretical treatments of boundary free energies (between proteins and lipids, and between solid and fluid phase lipids). 

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