Communication: Non-monotonic supersaturation dependence of the nucleus size of crystals with anisotropically interacting molecules

Bingham, Ruth; Rizzi, L. G.; Cabriolu, Raffaela; Auer, Stefan

doi:10.1063/1.4861044

Cited by 15 publications

(14 citation statements)

References 36 publications

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“…As illustrated in Figure 2, no fibrils can nucleate when the peptide concentration C < C e , whereas for C > C 1β the fibril nucleus is a single peptide and fibrils form in the absence of any nucleation barrier 4,10,11,45,50,51 . Importantly, for intermediate concentrations, C e < C < C 1β , fibril nucleation and elongation depends on their thickness 41 . Despite the fundamental importance of those expressions, they have not yet been verified by neither simulations nor experiments.…”

Section: Peptide Modelmentioning

confidence: 99%

Amyloid Fibril Solubility

Rizzi

Auer

2015

J. Phys. Chem. B

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It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain side-chain interactions, backbone hydrogen bonding and temperature affect amyloid fibril solubility, which might prove a powerful tool to design protein fibrils with desired solubility and aggregation properties in general.

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Section: Peptide Modelmentioning

confidence: 99%

Amyloid Fibril Solubility

Rizzi

Auer

2015

J. Phys. Chem. B

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“…Recent simulation and theoretical studies of fibril nucleation have highlighted that introducing an interaction anisotropy in these models results in a non-standard nucleation mechanism where the concept of a well-defined nucleus size breaks and nuclei with varying size are observed instead. [62][63][64] B. Pre-equilibrium kinetic models of spontaneous fibril nucleation Worth mentioning at this point are pre-equilibrium kinetic models of fibril nucleation, which often correspond to direct polymerization mechanisms. These models are characterized by two main assumptions.…”

Section: A Direct Polymerization Models Of Spontaneous Fibril Nucleat...mentioning

confidence: 99%

Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation

Šarić

Michaels

Zaccone

et al. 2016

The Journal of Chemical Physics

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Nucleation processes are at the heart of a large number of phenomena, from cloud formation to protein crystallization. A recently emerging area where nucleation is highly relevant is the initiation of filamentous protein self-assembly, a process that has broad implications in many research areas ranging from medicine to nanotechnology. As such, spontaneous nucleation of protein fibrils has received much attention in recent years with many theoretical and experimental studies focussing on the underlying physical principles. In this paper we make a step forward in this direction and explore the early time behaviour of filamentous protein growth in the context of nucleation theory. We first provide an overview of the thermodynamics and kinetics of spontaneous nucleation of protein filaments in the presence of one relevant degree of freedom, namely the cluster size.In this case, we review how key kinetic observables, such as the reaction order of spontaneous nucleation, are directly related to the physical size of the critical nucleus. We then focus on the increasingly prominent case of filament nucleation that includes a conformational conversion of the nucleating building-block as an additional slow step in the nucleation process. Using computer simulations, we study the concentration dependence of the nucleation rate. We find that, under these circumstances, the reaction order of spontaneous nucleation with respect to the free monomer does no longer relate to the overall physical size of the nucleating aggregate but rather to the portion of the aggregate that actively participates in the conformational conversion. Our results thus provide a novel interpretation of the common kinetic descriptors of protein filament formation, including the reaction order of the nucleation step or the scaling exponent of lag times, and put into perspective current theoretical descriptions of protein aggregation.2

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“…Two-step nucleation of polymorphic fibrils, and fibril polymorphism that occurs during fibril growth, or is determined by fibril growth, are not considered. Recently, our simulations showed that amyloid fibril nucleation occurring by direct polymerization of monomers is a peculiar kind of nucleation that does not comply with standard nucleation theory (45,46), because the concept of the existence of a critical nucleus breaks down (the nucleus size does not have a unique value) and there exist jumps in the nucleation rate of many orders of magnitude at certain concentrations (47,48). This called for the development of a new description of amyloid fibril nucleation that is able to describe this nonstandard nucleation of amyloid fibrils (30,49).…”

Section: Introductionmentioning

confidence: 99%

Nucleation of Polymorphic Amyloid Fibrils

Auer

2015

Biophysical Journal

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One and the same protein can self-assemble into amyloid fibrils with different morphologies. The phenomenon of fibril polymorphism is relevant biologically because different fibril polymorphs can have different toxicity, but there is no tool for predicting which polymorph forms and under what conditions. Here, we consider the nucleation of polymorphic amyloid fibrils occurring by direct polymerization of monomeric proteins into fibrils. We treat this process within the framework of our newly developed nonstandard nucleation theory, which allows prediction of the concentration dependence of the nucleation rate for different fibril polymorphs. The results highlight that the concentration dependence of the nucleation rate is closely linked with the protein solubility and a threshold monomer concentration below which fibril formation becomes biologically irrelevant. The relation between the nucleation rate, the fibril solubility, the threshold concentration, and the binding energies of the fibril building blocks within fibrils might prove a valuable tool for designing new experiments to control the formation of particular fibril polymorphs.

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Communication: Non-monotonic supersaturation dependence of the nucleus size of crystals with anisotropically interacting molecules

Abstract: Communication: Multicanonical entropy-like solution of statistical temperature weighted histogram analysis

Cited by 15 publications

References 36 publications

Amyloid Fibril Solubility

Amyloid Fibril Solubility

Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation

Nucleation of Polymorphic Amyloid Fibrils

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