14 research outputs found
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 × 10<sup>6</sup> s<sup>–1</sup>. 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><sub>2</sub>) 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><sub>1</sub> 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