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Modeling generic aspects of ideal fibril formation

Abstract : Many different proteins self-aggregate into insoluble fibrils growing apically by reversible addition of elementary building blocks. But beyond this common principle, the modalities of fibril formation are very disparate, with various intermediate forms which can be reshuffled by minor modifications of physico-chemical conditions or amino-acid sequences. To bypass this complexity, the multifaceted phenomenon of fibril formation is reduced here to its most elementary principles defined for a linear prototype of fibril. Selected generic features, including nucleation, elongation, and conformational recruitment, are modeled using minimalist hypotheses and tools, by separating equilibrium from kinetic aspects and in vitro from in vivo conditions. These reductionist approaches allow to bring out known and new rudiments, including the kinetic and equilibrium effects of nucleation, the dual influence of elongation on nucleation, the kinetic limitations on nucleation and fibril numbers, and the accumulation of complexes in vivo by rescue from degradation. Overlooked aspects of these processes are also pointed: the exponential distribution of fibril lengths can be recovered using various models because it is attributable to randomness only. It is also suggested that the same term "critical concentration" is used for different things, involved in either nucleation or elongation
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01263103
Contributor : Laurent Jonchère <>
Submitted on : Wednesday, January 27, 2016 - 1:55:06 PM
Last modification on : Friday, November 29, 2019 - 1:48:05 AM

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Denis Michel. Modeling generic aspects of ideal fibril formation. Journal of Chemical Physics, American Institute of Physics, 2016, 144 (3), pp.035101. ⟨10.1063/1.4940149⟩. ⟨hal-01263103⟩

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