Polymeric fibrils

Highly porous fabric stmetures, eg, Gore-Tex, that can be used as membranes have been developed by exploiting the unique fibrillation capabiHty of dispersion-polymerized PTFE (113). 

In the case of grinding, the cellulose fibers go over a state of fine fibrillation into a more or less powdery substance. This mechanical severance of cellulose may break main valence bonds and will, therefore, decrease its degree of polymerization. In addition, the crystal structure of cellulose fibers is nearly lost [32]. Grinding of the cellulose fibers also, appreciably increases its surface area. 

Several pathological self-polymerizing systems have been biophysi-cally characterized sufficiently to permit identification of protein or peptide species that could serve as molecular targets in a structure-activity relationship. These include transthyretin (TTR) [73-76], serum amyloid A protein (SAA) [77], microtubule-associated protein tau [78-80], amylin or islet amyloid polypeptide (IAPP) [81,82], IgG light chain amyloidosis (AL) [83-85], polyglutamine diseases [9,86], a-synuclein [47,48] and the Alzheimer s (3 peptide [87-96]. A variety of A(3 peptide assay systems have been established at Parke-Davis to search for inhibitors of fibril formation that could be therapeutically useful [97]. 

In the search for fibril formation inhibitors, the self-association to form amyloid fibrils of the A(3 peptides containing 40 and 42 amino acids can be treated as a coupled protein folding and polymerization process passing through multiple intermediate peptide species. The in vitro challenge is (1) to identify the various conformational forms and... 

Tau protein interacts with many other proteins that can contribute to abnormal fibrillogenesis. One example is a-synuclein, which induces fibrillization of tau. Coincubation of a-synnclein and tau synergistically promotes fibrillization of both proteins in vitro. Mice with a-synuclein mutation or a tau mutation exhibit filamen-tons inclusions of both proteins, which are abundant neuronal proteins that normally adopt an nnfolded conformation but polymerize into amyloid fibrils in... 

D-penidllamine can promote the elimination of copper (e.g., in Wilson s disease) and of lead ions. It can be given orally. Two additional uses are cystinu-ria and rheumatoid arthritis. In the former, formation of cystine stones in the urinary tract is prevented because the drug can form a disulfide with cysteine that is readily soluble. In the latter, penicillamine can be used as a basal regimen (p. 320). The therapeutic effect may result in part from a reaction with aldehydes, whereby polymerization of collagen molecules into fibrils is inhibited. Unwanted effects are cutaneous damage (diminished resistance to mechanical stress with a tendency to form blisters), nephrotoxicity, bone marrow depression, and taste disturbances. 

The threshold concentration of monomer that must be exceeded for any observable polymer formation in a self-assembling system. In the context of Oosawa s condensation-equilibrium model for protein polymerization, the cooperativity of nucleation and the intrinsic thermodynamic instability of nuclei contribute to the sudden onset of polymer formation as the monomer concentration reaches and exceeds the critical concentration. Condensation-equilibrium processes that exhibit critical concentration behavior in vitro include F-actin formation from G-actin, microtubule self-assembly from tubulin, and fibril formation from amyloid P protein. Critical concentration behavior will also occur in indefinite isodesmic polymerization reactions that involve a stable template. One example is the elongation of microtubules from centrosomes, basal bodies, or axonemes. 

The search for flexible, noncorrosive, inexpensive conductive materials has recently focused on polymeric materials. This search has increased to include, for some applications, nanosized fibrils and tubes. The conductivity of common materials is given in Figure 19.1. As seen, most polymers are nonconductive and, in fact, are employed in the electronics industry as insulators. This includes PE and PVC. The idea that polymers can become conductive is not new and is now one of the most active areas in polymer science. The advantages of polymeric conductors include lack of corrosion, low weight, ability to lay wires on almost a molecular level, and ability to run polymeric conductive wires in very intricate and complex designs. The topic of conductive carbon nanotubes has already been covered (Section 12.17). 

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