Proteins can feature ultrafast structural dynamics in the nanosecond timescale which are very challenging to measure using conventional techniques such as single-molecule Förster resonance energy transfer (smFRET). So far, the limited fluorescence brightness and the relatively long fluorescence lifetimes have limited the temporal resolution of smFRET to the 10 ns range. Moreover, these ultrafast smFRET measurements require very long acquisition times, often above several hours.
In a recent JACS publication in collaboration with the teams of Ben Shuler and Robert Best, the nanophotonic fluorescence enhancement in zero-mode waveguides is used to push forward the smFRET measurements of ultrafast protein dynamics in the low nanosecond range. The previously inaccessible dynamics of a short intrinsically disordered peptide were probed with nanosecond FCS and smFRET, paving the way to the investigation of very rapid biomolecular dynamics.
- The acquisition time needed for nanosecond FCS is reduced by more than one order of magnitude. Measurements that were taking several hours can now be performed in 20 minutes.
- The experimental data can be compared with all-atom molecular dynamics simulations, and used to further improve the accuracy of the numerical model.
- ZMWs from our group can be easily implemented in other labs with consistent optical performance.
G-quadruplex structures of DNA are promising target sites for anticancer therapy. However, the interaction of G-quadruplex with proteins remains poorly understood, notably the association and dissociation kinetics.
In a recent Nucleic Acid Research publication entitled “Fast interaction dynamics of G-quadruplex and RGG-rich peptides unveiled in zero-mode waveguides”, we use 120nm nanoapertures to measure the interaction dynamics between G-quadruplexes and peptides at micromolar concentration.
- The association and dissociation kinetics of the interaction are fully characterized for the first time and discussed in perspective of the nature and specificity of this interaction.
- Our approach using ZMW combined with FCCS-FRET opens up a new technique to investigate the previously unexplored interactions of DNA structures with a library of peptides at µM concentration. This is important to develop the antiviral and anticancer drug therapy applications involving G-quadruplexes.
We are opening a position for postdoctoral fellowship: experimental nanophotonics and plasmonic nano-optical tweezers. Read the details and apply through the CNRS institutional website: https://bit.ly/3HiobDC
Position filled and no longer available. Contact Jerome Wenger for enquiries.
Plasmonics can be used to enhance the emission properties of single quantum nano-objects and use them as bright ultrafast single photon sources. However, plasmonic trapping single quantum objects has remained highly challenging so far.
In a recent Nano Letters publication, we introduce a dedicated plasmonic nanoantenna design to trap single colloidal quantum dots and enhance their single photon emission. The nano-optical trapping automatically locates the quantum emitter at the nanoantenna hotspot where the emission enhancement is maximum.
Novelty and Impact:
- Enhanced single photon brightness is demonstrated from a trapped single quantum dot, together with strongly reduced blinking and accelerated lifetime. This provides a significant advance over previous reports lacking a clear demonstration of antibunching.
- Our novel nanoantenna design achieves the highest trap stiffness reported so far for individual quantum dots, allowing to reduce the trapping intensity and mitigate the thermal effects.
Preprint also freely available on ArXiv 2108.06508