Nucleation conformational

Serio TR, Cashikar AG, Kowal AS, Sawicki GJ, Moslehi JJ, Serpell L, Amsdorf MF, Lindquist SL (2000) Nucleated conformational conversion and the replication of conformational information by a prion determinant. Science 289 1317-1321... 

These observations were inconsistent with some aspect of each of the models previously proposed for amyloid hbrillogenesis (Serio et al., 2000). Thus, a new model, nucleated conformational conversion, was proposed (Serio et al., 2000). According to this model, fibers arise de novo from nuclei formed during the lag phase. These nuclei are structured, stable complexes of NM formed when structurally molten, oligomeric complexes undergo a conformational rearrangement during the lag... 

Fig.8. Nucleated conformational conversion model. S, state protein jagged spheres A-state protein dark, smooth spheres recently converted A-state protein light, smooth spheres. See text for details of the models.

These observations suggest that NM nucleus formation occurs via a modified version of NP (Serio et al, 2000). The A-state is apparently so unstable or rare in solution that it cannot be detected directly by the biochemical means described previously or indirectly through a concentration-dependent lag phase. However, A-state protein may be stabilized in the context of an unstructured NM oligomer, or molten prenucleus. Once stabilized, this prenucleus converts to a bona fide A-state nucleus that is then competent to assemble and direct the conformational conversion of soluble. S-state protein. Thus, the complete model that describes both NM nucleus formation, and its subsequent assembly onto preformed nuclei is a hybrid of both NP and TA. We refer to this model as nucleated conformational conversion or NCC (Fig. 8) (Serio et al, 2000). 

Experimental results are in general conformity with the Avrami equation, but the interpretation of various observations is still complicated in many instances. One intriguing observation is that the induction period for nucleation is inversely proportional to the length of time the liquid is held in the liquid state after previous melting. This dependence on prior history may be qualitatively understood... 

Homogeneous nucleation occurs when, as a result of statistically random segmental motion, a few segments have adopted the same conformation as they would have in a crystallite. At one time it was considered that the likelihood of the formation of such nuclei was greatest just above the transition temperature... 

Alzheimer s Disease. Figure 1 A(3 monomers can self-associate to form dimers, trimers and higher oligomers. Globular structures of synthetic A(342 are known as A(3-derived diffusible ligands (ADDLs) (3-12-mers of A(3). These structures are similar to the smallest protofibrils and represent the earliest macromolecular assembly of synthetic A(3. The characteristic amyloid fiber exhibits a high beta-sheet content and is derived in vitro by a nucleation-dependent self-association and an associated conformational transition from random to beta-sheet conformation of the A(3 molecule. Intermediate protofibrils in turn self-associate to form mature fibers. 

In particular, blends of PVDF with a series of different polymers (polymethylmethacrylate [100-102], polyethylmethacrylate [101], polyvinyl acetate [101]), for suitable compositions, if quenched from the melt and then annealed above the glass transition temperature, yield the piezoelectric [3 form, rather than the normally obtained a form. The change in the location of the glass transition temperature due to the blending, which would produce changes in the nucleation rates, has been suggested as responsible for this behavior. A second factor which was identified as controlling this behavior is the increase of local /rans-planar conformations in the mixed amorphous phase, due to specific interactions between the polymers [102]. 

Theoretical models available in the literature consider the electron loss, the counter-ion diffusion, or the nucleation process as the rate-limiting steps they follow traditional electrochemical models and avoid any structural treatment of the electrode. Our approach relies on the electro-chemically stimulated conformational relaxation control of the process. Although these conformational movements179 are present at any moment of the oxidation process (as proved by the experimental determination of the volume change or the continuous movements of artificial muscles), in order to be able to quantify them, we need to isolate them from either the electrons transfers, the counter-ion diffusion, or the solvent interchange we need electrochemical experiments in which the kinetics are under conformational relaxation control. Once the electrochemistry of these structural effects is quantified, we can again include the other components of the electrochemical reaction to obtain a complete description of electrochemical oxidation. 

After polarization to more anodic potentials than E the subsequent polymeric oxidation is not yet controlled by the conformational relaxa-tion-nucleation, and a uniform and flat oxidation front, under diffusion control, advances from the polymer/solution interface to the polymer/metal interface by polarization at potentials more anodic than o-A polarization to any more cathodic potential than Es promotes a closing and compaction of the polymeric structure in such a magnitude that extra energy is now required to open the structure (AHe is the energy needed to relax 1 mol of segments), before the oxidation can be completed by penetration of counter-ions from the solution the electrochemical reaction starts under conformational relaxation control. So AHC is the energy required to compact 1 mol of the polymeric structure by cathodic polarization. Taking... 

In order to relax 1 mol of compacted polymeric segments, the material has to be subjected to an anodic potential (E) higher than the oxidation potential (E0) of the conducting polymer (the starting oxidation potential of the nonstoichiometric compound in the absence of any conformational control). Since the relaxation-nucleation processes (Fig. 37) are faster the higher the anodic limit of a potential step from the same cathodic potential limit, we assume that the energy involved in this relaxation is proportional to the anodic overpotential (rj)... 

Figure 37. Lateral section of a polymeric film during the nucleation and growth of the conducting zones after a potential step. (Reprinted from T. F. Otero, H.-J. Grande, and J. Rodriguez, A new model for electrochemical oxidation of polypyrrole under conformational relaxation control. /. Electroanal. Chem. 394, 211, 1995, Figs. 2-5. Copyright 1995. Reprinted with permission from Elsevier Science.)...

In order to obtain the current consumed during the nucleated relaxation process under a constant potential, we assume that a stationary density of charge (<, ) will be stored in the polymer at the polarization potential E. The storage of these charges is controlled by both conformational relaxation (3r) and diffusion ( processes, so... 

Equations (57) and (58) describe the electrochemical oxidation of conducting polymers during the anodic potential sweep voltammograms (/f vs. q) or coulovoltagrams (Qr vs. tj) under conformational relaxation control of the polymeric entanglement initiated by nucleation in the reduced film. They include electrochemical variables and structural and geometric magnitudes related to the polymer. 

The use of ordered supramolecular assemblies, such as micelles, monolayers, vesicles, inverted micelles, and lyotropic liquid crystalline systems, allows for the controlled nucleation of inorganic materials on molecular templates with well-defined structure and surface chemistry. Poly(propyleneimine) dendrimers modified with long aliphatic chains are a new class of amphiphiles which display a variety of aggregation states due to their conformational flexibility [38]. In the presence of octadecylamine, poly(propyleneimine) dendrimers modified with long alkyl chains self-assemble to form remarkably rigid and well-defined aggregates. When the aggregate dispersion was injected into a supersaturated... 

Prion diseases resulting in encephalopathy can be transmitted between individuals within species (more rarely between species) [26-28], A conformational variant of the normal cellular protein PrPs (PrPc) (protease-sensitive or cellular) is believed to catalyze [29] or nucleate [30-33] conversion to the pathological form, PrPR (protease-resistant). This highly unusual nongenetic mode of transmission of an infectious agent has been strongly debated [29]. The observation of multiple examples of nucleated catalysis of aberrant polymerization of protein subunits has... 

As described earlier, Doi s kinetic theory leads to a prediction that the SD is triggered by extension of unoriented crystalline sequences prior to crystal nucleation. In order to confirm this prediction the conformational change... 

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