Discoidal molecules

Thermotropic liquid crystals can then be furflier subdivided into high molecular mass, main and side-chain polymers [10] and low molecular mass, the latter class of compounds being one of the areas of this review. The phases exhibited by the low molecular mass molecules are then properly described with reference to the symmetry and/or supramolecular geometry of the phases, which are briefly introduced here and are discussed in more detail further below. Thus, the most disordered mesophase is the nematic (N), which is found for calamitic molecules (N), discoidal molecules (Nq) and columnar aggregates (Nc), among others. The more ordered lamellar or smectic phases (S) [11, 12] are commonly shown by calamitic molecules, and there exists a variety of such phases distinguished by a subscripted letter (e. g. Sa, Sb)- Columnar phases (often, if incorrectly, referred to as discotic phases) may be formed from stacks of disc-like molecules, or from... 

FIGURE 2-7 Putative model of apoE in rHDL. Two molecules of apoE of a total of about four molecules per discoidal particle are depicted to circumscribe the periphery of a bilayer of phospholipids. The helical axes are orientated perpendicular to the phospholipid fatty acyl chains. Adapted from [36] with permission. 

Equation 8.7 [6] was obtained to correlate the experimental data on membrane plasmapheresis, which is the MF of blood to separate the blood cells from the plasma. The filtrate flux is affected by the blood velocity along the membrane. Since, in plasmapheresis, all of the protein molecules and other solutes will pass into the filtrate, the concentration polarization of protein molecules is inconceivable. In fact, the hydraulic pressure difference in plasmapheresis is smaller than that in the UF of plasma. Thus, the concentration polarization of red blood cells was assumed in deriving Equation 8.7. The shape of the red blood cell is approximately discoid, with a concave area at the central portion, the cells being approximately 1-2.5 pm thick and 7-8.5 pm in diameter. Thus, a value of r (= 0.000257 cm), the radius of the sphere with a volume equal to that of a red blood cell, was used in Equation 8.7. 

Apolipoprotein A-I is the primary protein component of HDL.23 2513 Most of the 243 residues consist of a nearly continuous amphipathic a helix with kinks at regularly spaced proline residues.26 28 Two disulfide-linked ApoA-I molecules may form a belt that encircles the discoid lipoprotein.2513 ApoA-II is the second major HDL protein, but no dearly specialized function has been identified.29 30 ApoA-I, II, and IV, apoC-I, II, and III, and apoE all have multiple repeats of 22 amino acids with sequences that suggest amphipathic helices. Tire 391-residue ApoA-IV has 13 tandem 22-residue repeats. Proline and glycine are present in intervening hinge regions.23 This may enable these proteins to spread over and penetrate the surfaces of the lipoprotein micelles. Most of these proteins are encoded by a related multigene family.7 303... 

Large ruminant platelets, including cattle, goats, and sheep, are similar in stmcture and function. Bovine platelets have been studied most extensively. Resting bovine platelets are discoid in shape and vary between 1 and 5 pm in diameter. Bovine platelets contain a few large alpha granules and dense bodies and have a dense tubular system, but lacks an open canalicular system (Zucker-Franklin et al. 1985 White 1987). Lack of an open canalicular system probably is responsible for altered function of bovine platelets. Surfiice-activated bovine platelets produce pseudopods but do not spread as do platelets of other species (Grouse et al. 1990). Further, ycoprotein Ilbllla molecules do not concentrate in the center of surfiice-activated bovine platelet as fiiey do in human platelets. 

Very few data exist for the viscosities or Frank constants of discotic nematics—that is, nematics composed of disc-Uke particles or molecules (Chandrasekhar 1992). One can estimate values of the Leslie viscosities from the Kuzuu-Doi equations (10-20) by setting the aspect ratio p equal to the ratio of the thickness to the diameter of the particles thus /j — 0 for highly anisotropic disks. This implies that R(p) —1, and Eq. (10-20b) implies that the viscosity o 2 is large and positive for discoidal nematics, while it is negative for ordinary nematics composed of prolate molecules or particles. If, as expected, is much smaller in magnitude than 0 2. the director (which is orthogonal to the disks) will tend... 

The hinged-domain hypothesis was developed from the characterization of discoidal particles formed between apoA-I and dimyristoyl-phosphatidylcholine (Brouillette et al., 1984). At different proteintDMPC molar ratios, several discretely sized particles were found in complexes containing a constant number of apoA-I molecules per particle. The stepsize between the particles was constant and the change in circumference of the discoidal particles was found equal to the diameter of two a helices (Brouillette et ai, 1984). Thus it was proposed that conformational changes in apoA-I that result in the all-or-none binding of complete a-helical domains controlled particle sizes formed. This size quantization of particle classes has since been shown to be a general characteristic of human apoA-I-lipid complexes reconstituted with a variety of phospholipids in the presence and absence of cholesterol. 

Figure 3. Two particle models used to calculate the theoretical scattered intensity. (A) = the discoid (B) = the closed lamella (o) water molecule ( ) s oxyethylene chain ...

Lipoproteins are often called pseudomicellar because their outer shell is in part composed of amphipathic phospholipid molecules. Unlike simple micelles, lipoproteins contain apolipoproteins, or apoproteins, in their outer shell and a hydrophobic core of triacylglycerol and cholesteryl esters. Unesterified, or free, cholesterol, which contains a polar group, can be found as a surface component and in the region between the core and surface (Figure 20-1). Most lipoproteins are spherical. However, newly secreted high-density lipoproteins (HDLs) from the liver or intestine are discoidal and require the action of lecithin-cholesterol acyltransferase (LCAT) in plasma to expand their core of neutral lipid and become spherical. The hydrophobic core of the low-density lipoprotein (LDL) molecule may contain two concentric layers one of triacylglycerol and another of cholesteryl ester. 

LCAT) [3,4], The pre-p HDL fraction in human plasma contains discoidal particles containing two or three molecules of apo A1 (cf. Section 4.3) with molecular masses in excess of 300 kDa. A smaller component of the pre-P HDL fraction comprises lipid-free/ poor apo A1 molecules, perhaps present in the monomeric state. 

Reconstituted spherical HDL can be made by co-sonication of selected HDL components (e.g., apo Al, PC, CE) or by extensively reacting discoidal reconstituted HDL with LCAT in the presence of an exogenous source of cholesterol. The products are spheroidal and, like the discoidal precursor particles, contain two, three, or four apo Al molecules per particle, PC, cholesterol, and a CE core. The diameters of the particles range from 80 to 120 A. Although not well studied, the conformation of apo Al appears distinct from that in the discoidal particles and is variable depending on the particle diameter (A. Jonas, 1990 M.G. Sorci-Thomas, 2002). 

In reconstituted discoidal HDL, the apolipoproteins form a protective shell, one-helix thick, around the periphery of the discs. The organization of apo Al molecules in such particles has been studied extensively using various spectroscopic techniques, as well as chemical cross-linking and mass spectrometry methods [21,22], There is general agreement that the a-helices of apo Al are aligned perpendicular to the PL acyl chains (Fig. 6A). The precise registry of the apolipoprotein helices is dependent upon the size of the disc, and various models to account for this effect have been proposed [21,22]. The nascent HDL particles created by ABCAl-mediated efflux of cellular PL and cholesterol to apo Al are discoidal with structures like those depicted in Fig. 6B (M.C. Phillips, 2(X)6). 

Fig. 6. Organization of apolipoprotein molecules in discoidal HDL particles. (A) Double belt model for apo A1 structure at the edge of discoidal HDL complex. Two ring-shaped molecules of apo A1 are stacked on top of each other with both molecules in an anti-parallel orientation, allowing the helix registry to maximize intermolecular salt-bridge interactions. Only the charged residues at selected positions are explicitly displayed. (B) Model of apo E in discoidal HDL complex depicting the locations of engineered tryptophan residues on helix 4. Fluorescence from these amino acids was monitored to determine helix orientation. Two out of a total of about four mole-cules/particles of apo E are depicted in which the helical axes are oriented perpendicular to the PL acyl chains.

Fig. 7 shows the LCAT-induced conversion of a discoidal apo Al-PC HDL particle, in which the apo A1 molecules are organized according to the model in Fig. 6A, to a spherical... 

Fig. 7. Influence of neutral lipids (cholesteryl ester (CE) and triacylglycerol (TG)) on the shape of HDL particles. Cholesterol molecules in discoidal apo Al/PL particles are converted to CE by the action of LCAT. As CE molecules are relatively insoluble in the PL bilayer of the discoidal particle, they form a separate phase in the core of the particle. The oil-drop model of spherical HDL comprises a non-polar core of CE and TG molecules encapsulated by a surface monolayer of amphipathic a-helical apolipoprotein and PL molecules. The apo A1 amphipathic a-helices, FC and PL molecules are depicted as cylinders, oblongs, and circles with two tails, respectively. The picture is not drawn to scale.

Very little is yet known about how phospholipid binds to apo A1 in native HDL (Chapter 17). Studies of lipid binding by wild type and mutant apo A1 species in vitro suggested important roles for the first (N-terminal) and last (C-terminal) amphipathic helical repeats. Until recently, mature apo A1 isolated from serum HDL by delipidation, urea-denaturation, and dialysis was widely used as a surrogate for native lipid-free apo A1 and/or pre-beta,-HDL. It has become clear, however, that these molecules differ significantly in physical properties. For example, serum-derived apo A1 self-associates whereas pre-beta,-HDL does not. Serum-derived apo A1 can completely unfold to seal the edge of discoidal recombinant particles containing large amounts of phospholipids and cholesterol. In contrast pre-beta,-HDL is not converted to discoidal HDL by additional phospholipid transfer. 

Fig. 27. Chemical structures of non mesomorphic discoid compound and TNF molecule used for induction of columnar mesophase through charge transfer interaction...

When amphipathic molecules are dispersed in water, their hydrophobic parts (i.e., hydrocarbon chains) aggregate and become segregated from the solvent. This is a manifestation of the hydrophobic effect which comes about because of exclusion and hence ordering of water at the interface between these distinct types of molecule. Aggregates of amphipathic molecules can be located at a water-air boimdary (monolayers) (Fig. 3-24) however, only a small quantity of an amphipathic lipid dispersed in water can form a monolayer (unless the water is spread as a very thin film). The bulk of the lipid must then be dispersed in water as micelles (Fig. 3-24). In both of these structures the polar parts, or heads (O), of the lipid make contact with the water, while the nonpolar parts, or tails (=), are as far from the water as possible. Micelles can be spherical as shown in Fig. 3-24, but can also form ellipsoidal, discoidal, and cylindrical stmctures. 

Certain amphiphatic molecules arrange themselves in discoidal bilayered structures known as bicelles. The bicelles have highly anisotropy magnetic susceptibility and thus the property to align themselves in the magnetic field with the plane normal perpendicular to the field [434]. This results in a uniaxial medium suitable for... 

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