Influence of denaturants on amyloid β42 aggregation kinetics.

Amyloid formation is linked to devastating neurodegenerative diseases, motivating detailed studies of the mechanisms of amyloid formation. For Aβ, the peptide associated with Alzheimer's disease, the mechanism and rate of aggregation have been established for a range of variants and conditions and in bodily fluids. A key outstanding question is how the relative stabilities of monomers, fibrils and intermediates affect each step in the fibril formation process.

Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors.

Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition.

Author Correction: Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aβ42 peptide.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aβ42 peptide.

Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer's disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils.

Short-range smectic fluctuations and the flexoelectric model of modulated nematic liquid crystals.

We show that the flexoelectric model of chiral and achiral modulated nematics predicts the compression modulus that is by orders of magnitude lower than the measured values. The discrepancy is much larger in the chiral modulated nematic phase, in which the measured value of the compression modulus is of the same order of magnitude as in achiral modulated nematics, even though the heliconical pitch is by an order of magnitude larger. The relaxation of a one-constant approximation in the biaxial elastic model used for chiral modulated nematics does not solve the problem.