Reversibility, Water-Mediated Switching, and Directed Cell Dynamics

Physics – Condensed Matter – Soft Condensed Matter

Scientific paper

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Scientific paper

Reversible switching of the complex network dynamics of proteins is mimicked in selected network glasses and compacted small carbohydrate molecules. Protein transitions occur on long time scales ~ us -ms, evocative of the exponentially large viscosities found in glass-forming supercooled liquids just above the glass transition; in searching for mechanisms for reversibly slowed "geared activation", Kauzmann was led from proteins to glasses. I show here that selected network glasses and small carbohydrate molecules can be used to model such transitions, and elucidate in particular some universal aspects of tandem repeats. The human ankyrin tandem repeat D34, with a superhelical "coiled spring" structure which has 426 residues, folds reversibly and plastically. Such molecules are too large for present transition-state numerical simulations, currently limited to ~ 100 residues solvated by ~ 3000 water molecules for times ~ ns. The transition states of D34 exhibit a surprisingly simple collective ("geared") pattern when studied by fluorescence near its center, in samples modified mutageneously along its 12 helical repeats. One can understand this "plastic" pattern by taking advantage of a symmetric 45-atom carbohydrate molecular bridge to "cross over" from proteins to inorganic network glasses. There one easily identifies gears, and can show that the collective pattern is the signature of nonlocal, water-mediated [hydro(phobic/philic)] switching. Details of the transition patterns emerge from analyzing the amino acid alpha helical repeat sequences with water-only hydrophobicity scales. Freezing and melting of monolayer water films at physiological temperatures can enable ankyrin repeats to direct cell dynamics in muscles, membranes and cytoskeletons.

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