Dielectric measurement of two-dimentionally confined biomolecules at the nanoscale

Informations projet

Dielec2DBiomolecules

N° de convention de subvention: 842402

DOI

10.3030/842402

Projet clôturé

Date de signature de la CE 10 Avril 2019

Date de début 10 Septembre 2019

Date de fin 9 Septembre 2021

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 224 933,76

Contribution de l’UE

€ 224 933,76

Coordonné par

THE UNIVERSITY OF MANCHESTER
United Kingdom

Periodic Reporting for period 1 - Dielec2DBiomolecules (Dielectric measurement of two-dimentionally confined biomolecules at the nanoscale)

Période du rapport: 2019-09-10 au 2021-09-09

Résumé du contexte et des objectifs généraux du projet

Dielectric properties of biomolecules are known to influence macromolecular assembly and interactions. For example, it is well established that Coulomb forces play a crucial role in determining the DNA packaging and the binding affinity of clinically important molecules to a specific DNA sequence owing to the large charge density of DNA. Such forces in turn strongly depend on the molecular dielectric polarization (or dielectric constant) of DNA. Despite such a crucial role, dielectric properties of biomolecules has remained practically unexplored so far because measurements are challenging, hampered by the small size of the molecules and their interplay with their solvent.
Recently, our group in Manchester succeeded in measuring the dielectric constant of few water layers under strong confinement. This was achieved by developing a new experiment platform that couples two novel nanotechnologies: scanning dielectric microscopy (SDM), a scanning probe microscope capable of probing dielectric properties son the nanoscale, and two-dimensional (2D) materials technology, which allows fabricating atomically thin channels and 2D liquid cells. In this project, by building on our initial study on water molecules, we will extend it to the case of biomolecules. We will implement a novel experimental platform to measure dielectric polarization of biomolecules under 2D confinement by scanning dielectric microscopy. Specifically, the overall objectives of this research are:
- Design of new 2D liquid cells that allow scanning dielectric microscopy on confined biomolecules.
- Measurement and extraction of the dielectric properties of 2D confined biomolecules.
- Development of theoretical models and smart-data analysis software for the extraction of the dielectric properties of biomolecules under 2D confinement.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

In this project, we successfully designed and fabricated new 2D liquid cells for dielectric characterization of biomolecules under 2D confinement using scanning dielectric microscopy. The design of the 2D liquid cells is based on the 2D nanochannel design, previously introduced for water’s dielectric properties, which was obtained by patterning and stacking 2D crystals to form nanochannels of controlled thickness. Notably we succeeded to fabricate them despite great disruptions caused by the Covid19 pandemic. This caused the shutdown of our cleanrooms and labs for various months followed by their restricted access for most of the duration of this project.

We successfully carried out the experiments of structural and dielectric characterization of the 2D liquid cells that we fabricated and confined biomolecules using scanning dielectric microscopy. We developed novel numerical models for the 2D liquid cells and the biomolecules, and applied them to interpret our experimental data.

The extracted dielectric properties that we obtained in this project represent an important step forward in our understanding of dielectric properties of biomolecules under strong confinement. To achieve these results, we implemented contingency plans and modified the planning to limit the impact of the Covid19 pandemic, which caused great delays in the experiments. For this reason, the experiments are not fully completed yet. Dielectric characterization of the devices with confined biomolecules is still under progress and publications are in preparation. Notably, during this project, we obtained additional results, which already led to three publications in important peer-reviewed journals of the field in the period (plus one just accepted). In particular, we discovered the emergence of interfacial ferroelectricity in marginally twisted hexagonal boron nitride crystals, an important finding that we published in paper in a Nature journal in the period. This paper was also awarded the prize as best paper of the semester by the Spanish Royal Society of Physics, which gave additional highlight to these findings.

In addition to the dissemination through publications, Dr Fabregas presented the results as speaker to national and international conferences, including the One-Day Meeting for Early Career Biological Physicists 2020 (UK) and the International Conference of Nanoscience and Technology 2021 (Canada). He was also invited to give a seminar at the Department of Applied Mathematics of the University of Granada (Spain) and a course on COMSOL Multiphysics. Dr Fábregas also participated to outreach activities, including the MCAA Annual Conference and the gender and diversity day organized by the University of Manchester.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

As the project has come to its end, we can conclude that it was successful, having achieved most of its objectives and milestones in the period. Importantly, they were achieved despite major disruptions caused by the Covid19 pandemic, which had strong impact on this project given its experimental nature. We successfully produced novel 2D liquid cells with new 2D crystals, carried out more complex experiments and developed more complex numerical models than previously done, thus developing a new platform for measuring the dielectric properties of biomolecules under strong confinement - not simply water as previously done by the group.

The experimental findings obtained with this project are important and well beyond the state of the art. They provide new information on the dielectric properties of biomolecules, which had remained essentially unknown. This information will be crucial, as it will allow developing theories of biomolecular interactions and their assembly, thus improving our understanding of biomolecular systems on the atomic scale. Hence, we expect to publish the final results in three high-impact papers currently in preparation, in addition to three papers already published in the period (plus one just accepted). In addition, during this project, we made the important discovery of interfacial ferroelectricity in 2D crystals of hexagonal boron nitride when they are twisted by a small angle. This finding is a major advanced, as recognized by being published by a Nature journal. It opened up new possibilities for designing novel devices with ferroelectric properties based on 2D heterostructures and offered a new probe to visualize these properties.

This project has generated technological advances in many research areas, from Life sciences (molecular biology and biophysics) to Materials sciences (physics, chemistry and nanotechnology) with societal and socio-economic impact in the medium and long-term. They include the potential of developing new drugs against important diseases and of molecular sensing devices based on the newly developed measurement platform. The newly developed methods and theoretical models for scanning dielectric microscopy also represent a great advance in nanoscience and nanotechnology.

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