RESUMO
In this work we study the effect of solution ionic strength on the structural evolution of amidated amyloid beta peptide Aß (1-40) oligomers at the early stages of fibril formation. By light scattering, we follow the time evolution of the structure and short-time dynamics of peptide structures at low ionic strengths. Our results allow identifying initial oligomer structures as the effective building blocks in the amyloid fibrils formation and indicate that the oligomers growth pathway, from compact structures to flexible chain-like structures, becomes faster as the solution ionic strength is increased. Furthermore, we find no evidence of structural branching what suggests that elongation of amyloid fibrils is dominated by linear association. To describe our results we adapt a phenomenological model based on population balance equations and linear polymer growth, where the parameters required are obtained from the experiments. Model calculations are in good agreement with experimentally-obtained estimates for the radius of gyration of Aß (1-40) oligomers, thus further supporting our findings. Additionally, we introduce a model for the effective interaction among initial Aß structures that captures the dependence of the effective association rates on solution ionic strength.
Assuntos
Peptídeos beta-Amiloides/química , Fragmentos de Peptídeos/química , Peptídeos beta-Amiloides/síntese química , Cinética , Luz , Microscopia Eletrônica de Transmissão , Simulação de Dinâmica Molecular , Concentração Osmolar , Fragmentos de Peptídeos/síntese química , Estabilidade Proteica , Espalhamento de Radiação , Água/químicaRESUMO
We characterize the translational and rotational dynamics of birefringent spherical colloidal particles by depolarized light scattering in the far- and near-field regimes. For this purpose, we use depolarized dynamic light scattering and propose an extension of dynamic heterodyne near-field light scattering that takes into account the polarization state of the light. Such a combination of methods allows to access colloidal dynamics in an extended q-range and permits to evaluate different modes of particles motion in suspension. Furthermore, we obtain a good agreement between results from the far- and near-field approaches thus validating our proposal and opening the possibility to investigate simultaneously the subtle interplay between translational and rotational motions of anisotropic colloidal particles in length-scales from the order of the particle size to several interparticle distances.