A new era for understanding amyloid structures and disease

The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. The accumulation and deposition of amyloid fibrils, collectively known as amyloidosis, is associated with many pathological conditions that can be associated with ageing, such as Alzheimer disease, Parkinson disease, type II diabetes and dialysis-related amyloidosis. However, elucidation of the atomic structure of amyloid fibrils formed from their intact protein precursors and how fibril formation relates to disease has remained elusive. Recent advances in structural biology techniques, including cryo-electron microscopy and solid-state NMR spectroscopy, have finally broken this impasse. The first near-atomic-resolution structures of amyloid fibrils formed in vitro, seeded from plaque material and analysed directly ex vivo are now available. The results reveal cross-β structures that are far more intricate than anticipated. Here, we describe these structures, highlighting their similarities and differences, and the basis for their toxicity. We discuss how amyloid structure may affect the ability of fibrils to spread to different sites in the cell and between organisms in a prion-like manner, along with their roles in disease. These molecular insights will aid in understanding the development and spread of amyloid diseases and are inspiring new strategies for therapeutic intervention

Super-resolution Fluorescence Quenching Microscopy of Graphene

Lately, fluorescence quenching microscopy (FQM) has been introduced as a new tool to visualize graphene-based sheets. Even though quenching of the emission from a dye molecule by fluorescence resonance energy transfer (FRET) to graphene happens on the nanometer scale, the resolution of FQM so far is still limited to several hundreds of nanometers due to the Abbe limit restricting the resolution of conventional light microscopy. In this work, we demonstrate an advancement of FQM by using a super-resolution imaging technique for detecting fluorescence of color centers used in FQM. The technique is similar to stimulated emission depletion microscopy (STED). The combined “FRET+STED” technique introduced here for the first time represents a substantial improvement to FQM since it exhibits in principle unlimited resolution while still using light in the visible spectral range. In the present case we demonstrate all-optical imaging of graphene with resolution below 30 nm. The performance of the technique in terms of imaging resolution and contrast is well described by a theoretical model taking into account the general distance dependence of the FRET process and the distance distribution of donor centers with respect to the flake. In addition, the change in lifetime for partially quenched emitters allows extracting the quenching distance from experimental data for the first time

Nanoengineered Diamond Waveguide as a Robust Bright Platform for Nanomagnetometry Using Shallow Nitrogen Vacancy Centers

Photonic structures in diamond are key to most of its application in quantum technology. Here, we demonstrate tapered nanowaveguides structured directly onto the diamond substrate hosting shallow-implanted nitrogen vacancy (NV) centers. By optimization based on simulations and precise experimental control of the geometry of these pillar-shaped nanowaveguides, we achieve a net photon flux up to ∼1.7 × 10⁶ s^–1. This presents the brightest monolithic bulk diamond structure based on single NV centers so far. We observe no impact on excited state lifetime and electronic spin dephasing time (<i>T</i>₂) due to the nanofabrication process. Possessing such high brightness with low background in addition to preserved spin quality, this geometry can improve the current nanomagnetometry sensitivity ∼5 times. In addition, it facilitates a wide range of diamond defects-based magnetometry applications. As a demonstration, we measure the temperature dependency of <i>T</i>₁ relaxation time of a single shallow NV center electronic spin. We observe the two-phonon Raman process to be negligible in comparison to the dominant two-phonon Orbach process

Microwave-Assisted Cross-Polarization of Nuclear Spin Ensembles from Optically Pumped Nitrogen-Vacancy Centers in Diamond

The ability to optically initialize the electronic spin of the nitrogen-vacancy (NV) center in diamond has long been considered a valuable resource to enhance the polarization of neighboring nuclei, but efficient polarization transfer to spin species outside the diamond crystal has proven challenging. Here we demonstrate variable-magnetic-field, microwave-enabled cross-polarization from the NV electronic spin to protons in a model viscous fluid in contact with the diamond surface. Further, slight changes in the cross-relaxation rate as a function of the wait time between successive repetitions of the transfer protocol suggest slower molecular dynamics near the diamond surface compared to that in bulk. This observation is consistent with present models of the microscopic structure of a fluid and can be exploited to estimate the diffusion coefficient near a solid–liquid interface, of importance in colloid science