Pores formation

A salient feature of all known pores is their irreversible anchorage in the lipid bilayer (Bhakdi and Tranum-Jensen, 1987). Hence, membrane-bound PFTs must be amphiphilic, possessing a lipid binding surface and a hydrophilic face that lines the aqueous channel. The pore-forming domains themselves are unlikely to harbor extended stretches of hydrophobic amino acid residues. Rather, they would be expected to possess amphipathic secondary structure. Rules to identify or predict pore-forming sequences do not exist, and even the solution of the structure of a water-soluble protomer form will not permit conclusions to be drawn on the structure of the pore. This situation is given in the case of aerolysin (Parker et al., 1996). 

In sum, pores may be formed by the insertion of quite short amino acid sequences into the bilayer. These sequences should assume an amphipathic conformation. If oligomerization occurs, closed ring structures can be formed. In some cases, incomplete oligomerization leads to formation of heterogeneously sized arcs. It is also conceivable, although not yet proven, that some pore-formers act as monomers with corresponding variations in functional pore size. In the same context, such slit-opening polypeptide sequences may render possible the translocation of other protein domains across the bilayer, as is required for release of certain toxins from intracellular compartments. 

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Qualitative examples abound. Perfect crystals of sodium carbonate, sulfate, or phosphate may be kept for years without efflorescing, although if scratched, they begin to do so immediately. Too strongly heated or burned lime or plaster of Paris takes up the first traces of water only with difficulty. Reactions of this type tend to be autocat-alytic. The initial rate is slow, due to the absence of the necessary linear interface, but the rate accelerates as more and more product is formed. See Refs. 147-153 for other examples. Ruckenstein [154] has discussed a kinetic model based on nucleation theory. There is certainly evidence that patches of product may be present, as in the oxidation of Mo(lOO) surfaces [155], and that surface defects are important [156]. There may be catalysis thus reaction VII-27 is catalyzed by water vapor [157]. A topotactic reaction is one where the product or products retain the external crystalline shape of the reactant crystal [158]. More often, however, there is a complicated morphology with pitting, cracking, and pore formation, as with calcium carbonate [159]. 

Schmuki P, Lockwood D J, Bsiesy A and Isaacs FI S (eds) 1997 Pits and Pores Formation, Properties, and Significance for Advanced Luminescent Materials Proc. vol 97-7 (Pennington, NJ Electrochemical Society)... 

The stmcture of the nucleotide antibiotic, phosmidosine (185), isolated from the culture filtrates of Streptomjces sp. RK-16 has been elucidated (282). Phosmidosine inhibits pore formation of Botrytis cinerea 2mBA.spergillus niger... 

Aeromonas hydrophila is a bacterium that causes diarrheal diseases and deep wound infections. These complications arise due to pore formation in sensitive cells by the protein toxin aerolysin. Proteolytic processing of the 52-kD precursor proaerolysin (Figure 10.34) produces the toxic form of the protein, aerolysin. Like a-hemolysin, aerolysin monomers associate to form a heptameric transmembrane pore. Michael Parker and coworkers have proposed... 

Hugh.son, F., 1997. Penetrating in.sights into pore formation. Nature Structural Biology 4 89—92. 

Probably the only feature common to the mechanism of oxidation of the two groups is that, because of crack or pore formation in the continuous oxide, the rate of transport of oxygen in a molecular form has increased to the point where a phase-boundary reaction has assumed rate control. In... 

According to Eq. (23), the critical pore radius r greatly decreases with increasing electrode potential. It is seen that above a certain critical potential AE b the active barrier as well as the critical pore radius decreases steeply with anodic potential. This critical potential AE is the lowest potential of pore formation and below this potential the passive film is stable against electrocapillary breakdown because of an extremely high activation barrier and the large size of pore nucleus required. 

Figure 16. Activation barrier A for the formation of a breakthrough pore in a thin surface oxide film on metal as a function of electrode potential at two different surface tensions, om, of the metal/electrolyte interface.7The solid lines indicate the values of A b against Aand the dotted lines correspond to die critical potentials for the pore formation. ACd= 1 F m-2, a = 0.01 J m-2, h = 2 x 10-9 m, a, am = 0.41 J m 2 b, am 0.21 J m 2 (From N. Sato, J. Electmchem. Soc. 129, 255, 1982, Fig. 3. Reproduced by permission of The Electrochemical Society, Inc.)...

Lower-density E-plastomers have found alternate use in cast film processes to make elastic film laminates with good breathability which contain laminates of liquid impermeable extensible polymeric films with extensible-thermoplastic-polymer-fiber nonwovens and nonwoven webs of polyethylene-elastomer fibers as the intermediate layers. The development relates to a breathable film including an E-plastomer and filler that contributes to pore formation after fabrication and distension of the film. The method and extent of distension is designed to produce a breathable film by stretching the film to form micropores by separation of the film of the E-plastomer from the particulate solids. This film is useful for manufacture of absorbent personal-care articles, such as disposable diapers and sanitary napkins and medical garments. In detail, these constructions comprise a liquid impermeable extensible film comprising polyolefins. The outer layer contains extensible-thermoplastic-polymer-fiber nonwovens, and an elastic intermediate layer contains nonwoven webs of fiber E-plastomers. The intermediate layer is bonded to the film layer and the outer... 

Modeling Pardaxin Channel. The remarkable switching of conformation in the presence of detergents or phospholipid vesicles (5) suggests that pardaxin is a very flexible molecule. This property helps to explain the apparent ability of pardaxin to insert into phospholipid bilayers. In addition, it is consistent with the suggestion that the deoxycholate-like aminoglycosteroids (5,7) present in the natural secretion from which pardaxin is purified (5) serve to stabilize its dissociated conformation. The question of the mechanism by which pardaxin assembles within membranes is important for understanding pore formation and its cytolytic activity (5). 

We have developed a series of models in which 8-12 monomers were packed in an antiparallel manner to form the channel. The kinetics of pore formation in liposomes (9) and the dependence of planar bilayer conductance on toxin... 

Step 4 - Addition of the synthetic pardaxin (10 M) to the bath results after 10-20 min in tetramer insertion into the bilayer and pore formations as measured by the current fluctuations depicted in B at a positive potential of 100 mV. The single channel conductance can be estimated from the amplitude of the current steps divided by the applied voltage and was in the range of 10 pS. 

Although for the moment this model is only partially supported by experimental data it offers the opportunity to design new experiments which will help to understand the mechanisms of pardaxin insertion and pore formation in lipid bilayers and biological membranes which at a molecular level are the events leading to shark repellency and toxicity of this marine toxin. 

KDHRF A homologous restriction factor binds to C8 65KDHRF A homologous restriction factor, also known as C8 binding protein interferes with cell membrane pore-formation by C5b-C8 complex Kcat Catalytic constant a measure of the catalytic potential of an enzyme Ka Equilibrium dissociation constant kD Kilodalton Kd Dissociation constant KD Kallidin... 

The most developed and widely used approach to electroporation and membrane rupture views pore formation as a result of large nonlinear fluctuations, rather than loss of stability for small (linear) fluctuations. This theory of electroporation has been intensively reviewed [68-70], and we will discuss it only briefly. The approach is similar to the theory of crystal defect formation or to the phenomenology of nucleation in first-order phase transitions. The idea of applying this approach to pore formation in bimolecular free films can be traced back to the work of Deryagin and Gutop [71]. 

As has been described in Ref. 70, this approach can reasonably account for membrane electroporation, reversible and irreversible. On the other hand, a theory of the processes leading to formation of the initial (hydrophobic) pores has not yet been developed. Existing approaches to the description of the probability of pore formation, in addition to the barrier parameters F, y, and some others (accounting, e.g., for the possible dependence of r on r), also involve parameters such as the diffusion constant in r-space, Dp, or the attempt rate density, Vq. These parameters are hard to establish from first principles. For instance, the rate of critical pore appearance, v, is described in Ref. 75 through an Arrhenius equation ... 

It follows from previous discussion that the destabilizing electrostatic contribution grows in absolute value with x (with increasing A.). But the influence of the nonuniform electrical force is overwhelmed by the stabilizing bending and stretching contributions. As a result, the traditional smectic model cannot explain how a small transmembrane voltage can lead to membrane breakdown. The obvious solution is to abandon this approach and to develop an alternative, such as the pore formation model. However, as we noticed before, this approach postulates rather than proves the appearance of hydrophobic pores. 

In our approach to membrane breakdown we have only taken preliminary steps. Among the phenomena still to be understood is the combined effect of electrical and mechanical stress. From the undulational point of view it is not clear how mechanical tension, which suppresses the undulations, can enhance the approach to membrane instability. Notice that pore formation models, where the release of mechanical and electrical energy is considered a driving force for the transition, provide a natural explanation for these effects [70]. The linear approach requires some modification to describe such phenomena. One suggestion is that membrane moduli should depend on both electrical and mechanical stress, which would cause an additional mode softening [111]. We hope that combining this effect with nonlocality will be illuminating. 

Clustering of a certain number of CD4 and coreceptor molecules is presumed to be necessary for the efficient HIV-1 Env-mediated fusion pore formation. It has been proposed that four to six CCR5 molecules (91) and three CD4 binding events are needed to induce fusion between the viral and host cell membranes (92). Both CD4 (93) and chemokine receptors can form functional dimers (94) in the plasma membrane. It was proposed that formation of CD4 dimers, mediated by a disulfide bond between the cysteine residues of the D2 domain, might enhance HIV-1 entry and infection (95,96). In contrast, others have provided... 

Markosyan RM, Cohen FS, Melikyan GB. HIV-1 envelope proteins complete their folding into six-helix bundles immediately after fusion pore formation. Mol Biol Cell 2003 14(3) 926—938. 

Two questions that arise are, why does pore formation occur only after the compact oxide has reached a certain value and, once the dissolution starts, why is it not even ... 

The capacitance determined from the initial slopes of the charging curve is about 10/a F/cm2. Taking the dielectric permittivity as 9.0, one could calculate that initially (at the OCP) an oxide layer of the barrier type existed, which was about 0.6 nm thick. A Tafelian dependence of the extrapolated initial potential on current density, with slopes of the order of 700-1000 mV/decade, indicates transport control in the oxide film. The subsequent rise of potential resembles that of barrier-layer formation. Indeed, the inverse field, calculated as the ratio between the change of oxide film thickness (calculated from Faraday s law) and the change of potential, was found to be about 1.3 nm/V, which is in the usual range. The maximum and the subsequent decay to a steady state resemble the behavior associated with pore nucleation and growth. Hence, one could conclude that the same inhomogeneity which leads to pore formation results in the localized attack in halide solutions. 

When the results for oxide growth and anion incorporation172,160 are compared with the kinetics of space charge accumulation in barrier and porous alumina films [see Section IV(1)], it can be concluded that anion incorporation modifies the electrostatics of the external oxide interface, thus influencing oxide dissolution and pore formation.172... 

In the sixth paper of this chapter, Kierzek et al., mainly focus on modeling of pore formation vs surface area growth phenomena upon activation of coal and pitch-derived carbon precursors. These authors briefly touch on other precursor carbons as well. The properties of newly synthesized materials are being looked at from the point of view of their application as active materials in the supercapacitor electrodes. Editors thought this work by the Institute of Chemistiy and Technology of Petroleum and Coal in Poland, could be of genuine interest to the practical developers of carbon materials for the supercapacitor industry. 

Heuck, A.P., Savva, C.G., Holzenburg, A., and Johnson, A.E. (2007) Conformational changes that effect oligomerization and initiate pore formation are triggered throughout perfringolysin O upon binding to cholesterol./. Biol. Chem. 282, 22629-22637. 

Matsuzaki K, Murase O, Fujii N, Miyajima K (1996) An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry-Us 35 11361-11368... 

Hirakura, Y., and Kagan, B. L. (2001). Pore formation by beta-2-microglobulin A mechanism for the pathogenesis of dialysis associated amyloidosis. Amyloid 8, 94-100. 

Recent results indicate that not only topogenic signals and membrane composition contribute to the proper topology of a membrane protein. The antimicrobial peptide nisin, produced by Lactococcus lactis, kills Gram-positive bacteria via pore formation, thus leading to the permeabilisation of the membrane. Nisin depends on the cell-wall precursor Lipid II, which functions as a docking molecule to support a perpendicular stable transmembrane orientation [43]. 

Benz, R., Schmid, A., Nakae, T. and Yos-Scheperkeuter, G. H. (1986). Pore formation by LamB of Escherichia coli in lipid bilayer membranes, J. Bacteriol., 165, 978-986. 

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