Journal
LANGMUIR
Volume 28, Issue 15, Pages 6386-6395Publisher
AMER CHEMICAL SOC
DOI: 10.1021/la300143j
Keywords
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Funding
- U.S. DOE [ER15377]
- NASA under the NSF Center for Chemical Evolution [CHE-1004570]
- [NSF-CBC-0739189]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1004570] Funding Source: National Science Foundation
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [0907435] Funding Source: National Science Foundation
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Recent evidence suggests that simple peptides can access diverse amphiphilic phases, and that these structures underlie the robust and widely distributed assemblies implicated in nearly 40 protein misfolding diseases. Here we exploit a minimal nucleating core of the A beta peptide of Alzheimer's disease to map its morphologically accessible phases that include stable intermolecular molten particles, fibers, twisted and helical ribbons, and nanotubes. Analyses with both fluorescence lifetime imaging microscopy (FLIM) and transmission electron microscopy provide evidence for liquid-liquid phase separations, similar to the coexisting dilute and dense protein-rich liquid phases so critical for the liquid-solid transition in protein crystallization. We show that the observed particles are critical for transitions to the more ordered cross-beta peptide phases, which are prevalent in all amyloid assemblies, and identify specific conditions that arrest assembly at the phase boundaries. We have identified a size dependence of the particles in order to transition to the para-crystalline phase and a width of the cross-beta assemblies that defines the transition between twisted fibers and helically coiled ribbons. These experimental results reveal an interconnected network of increasing molecularly ordered cross-beta transitions, greatly extending the initial computational models for cross-beta assemblies.
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