121 research outputs found
Inhibition of alpha-Synuclein Fibril Elongation by Hsp70 Is Governed by a Kinetic Binding Competition between alpha-Synuclein Species
No full textHeterogeneity of social cognition between visual perspective-taking and theory of mind in the temporo-parietal junction
No full textVisual perspective taking (VPT), particularly level 2 VPT (VPT2), which allows an individual to understand that the same object can be seen differently by others, is related to the theory of mind (ToM), because both functions require a decoupled representation from oneself. Although previous neuroimaging studies have shown that VPT2 and ToM activate the temporo-parietal junction (TPJ), it is unclear whether common neural substrates are involved in both functions. To clarify this point, we directly compared the TPJ activation patterns of individual participants performing VPT2 and ToM tasks using functional magnetic resonance imaging and within-subjects design. A whole-brain analysis revealed that VPT2 and ToM activated overlapping areas in the posterior part of the TPJ. In addition, we found that both the peak coordinates and activated regions for ToM were located significantly more anteriorly and dorsally within the bilateral TPJ than those measured during the VPT2 task. We further confirmed that these activated areas were spatially distinct from the nearby extrastriate body area (EBA), visual motion area (MT+), and the posterior superior temporal sulcus (pSTS) using independent localizer scans. Our findings revealed that VPT2 and ToM have gradient representations, indicating the functional heterogeneity of social cognition within the TPJ
Strength of nanotubes, filaments, and nanowires from sonication-onduced scission
No full textA model to describe the cavitation-induced breakage of nanofilaments during their sonication in solution is proposed. The model predicts a limiting length below which scission no longer occurs, and accurately describes experimental results for materials ranging from carbon nanotubes to protein fibrils. Sonication-induced breakage can now be used as a probe for the strength of nanostructures. © 2009 WILEY-VCH Verlag GmbH & Co. KGaA
Physical mechanisms of amyloid nucleation on fluid membranes
No full textBiological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein-membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways-protein-rich and lipid-rich-and quantify how the membrane fluidity and protein-membrane affinity control the relative importance of those molecular pathways. We find that the membrane's susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterize the rates and the free-energy profile associated with this heterogeneous nucleation process, in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalyzed amyloid aggregation of α-synuclein, a protein implicated in Parkinson's disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context
Multiphase Protein Microgels
No full textPeptides and proteins represent attractive building blocks for the development of new functional materials due to the biocompatibility and biodegradability of many naturally abundant proteins. In nature, sophisticated material functionality is commonly achieved through spatial control of protein localisation and structure on both the nano and micro scales. We approached this requirement in an artificial setting by exploiting the propensity of proteins to self-assemble into amyloid fibrils to achieve nano scale order, and utilised aqueous liquid/liquid phase separation to control the micron scale localization of the proteinaceous component under microconfinement. We show that in combination with droplet microfluidics, this strategy allows the synthesis of core-shell microgel particles composed of protein nanofibrils
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