Intramolecular optical microscopy with sub-nm spatial resolution in single biomolecules and single-protein sequencing

Projektinformationen

IntraMol

ID Finanzhilfevereinbarung: 101065980

DOI

10.3030/101065980

Projekt abgeschlossen

EK-Unterschriftsdatum 22 August 2022

Startdatum 1 Januar 2023

Enddatum 31 Dezember 2024

Finanziert unter

• Marie Skłodowska-Curie Actions (MSCA)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 173 847,36

Koordiniert durch

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

Periodic Reporting for period 1 - IntraMol (Intramolecular optical microscopy with sub-nm spatial resolution in single biomolecules and single-protein sequencing)

Berichtszeitraum: 2023-01-01 bis 2024-12-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Advancements in biomedical research rely heavily on our ability to visualize biological structures at the smallest possible scale. Traditional optical microscopy is limited by the diffraction of light (approx. 200 nm), making it impossible to resolve molecular structures with atomic precision. Super-resolution microscopy can overcome this barrier but it is still limited to around 10-20 nm in resolution. This project overcomes that limitation by developing Ångström-resolution fluorescence microscopy (Resolution Enhancement by Sequential imaging - RESI), a revolutionary technique capable of visualizing biomolecular interactions at a scale previously thought unattainable.

By achieving a localization precision of approximately 1 Ångström (0.1 nanometers), this technique enables researchers to directly observe molecular arrangements, protein interactions, and structural changes in biological systems with unprecedented clarity. Such insights have profound implications for drug discovery, disease diagnostics, and the development of targeted therapies.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

The project focused on developing a revolutionary microscopy technique to achieve, for the first time, Ångström resolution with an optical microscope. By leveraging the precise blinking behavior of fluorescent molecules, sequential super-resolution imaging and implementing sophisticated localization algorithms, we achieved a resolution far beyond what was previously possible with standard super-resolution methods.

Key achievements include:
• The direct visualization of biomolecular distances at the atomic scale.
• Demonstration of RESI’s ability to resolve molecular changes in biological systems, offering insights into protein conformations and interactions.
• Application of the technique to biomedical research, showing its potential for studying disease mechanisms at an unprecedented level of detail.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

This work represents a major leap beyond the current state of the art in microscopy. Existing super-resolution techniques, such as STED and DNA-PAINT, achieve resolutions in the nanometer range, but RESI pushes the boundary to the Ångström scale. This advance opens new doors for structural biology and biomedical research, enabling direct visualization of molecular processes that drive health and disease.

To fully leverage RESI’s potential, future developments will focus on broader accessibility and adaptation for live-cell imaging, integration with other imaging modalities, and further refinement for biomedical applications. These advancements will accelerate discoveries in molecular biology, drug development, and personalized medicine.

Ångström-resolution fluorescence microscopy in synthetic nanostructures and biological samples.