Skip to ContentSkip to Navigation
Research Zernike (ZIAM) News

Contact formation at the nanoscale: How do viral proteins reach out to start self-assembly?

09 November 2021

The formation of viruses is a beautiful example of how nature creates fascinatingly efficient, and often also very dangerous, protein-based nanoparticles. Despite the huge impact of viral diseases on society, it remains largely unclear how the process of viral self-assembly takes place. The team of Wouter Roos from the University of Groningen, together with colleagues from Amsterdam and the USA, has now unraveled the mechanism behind the first steps of virus self-assembly. The researchers used advanced microscopy techniques to visualize how viral proteins find each other and how they start constructing the virus particle. Their findings are published 3 November in the journal Science Advances.

Virus self assembly
Virus self assembly

Many supramolecular machines, including viruses, spontaneously self-assemble from their elementary components through a series of reactions into complex, nanosized particles. Nature beautifully controls this process through an optimized relation between all steps, thereby preventing mistakes. Maybe because it works so efficiently and fast, the process of self-assembly remains largely elusive, let alone that we can copy it in synthetic materials. Understanding self-assembly at the single-molecule level is necessary to unveil factors that modulate the efficiency and fidelity of the process. When we possess this knowledge, new avenues for antiviral intervention and molecular therapeutics will open up.

The reason that viral self-assembly remains elusive, is because established techniques are not able to capture the dynamics of the tiny components in this process. In order to elucidate the mechanisms behind assembly, real-time visualization at the single molecule level is needed. Here we combine the powerful single-molecule techniques of fluorescent optical tweezers (OT) with the nanoscale, fast imaging technique of high speed atomic force microscopy (HS-AFM). This allows us to scrutinize the first steps of capsid assembly and nucleic acid encapsidation of Hepatitis B Virus (HBV).

Wouter Roos
Wouter Roos

While it was postulated before that assembly should proceed via intense protein-protein contacts, Roos and his colleagues now elucidated the kinetics of this process. By determining the energy landscape of assembly initiation and recording movies of this nanosized process, it was revealed that indeed the first steps in viral self-assembly occur via so-called contact-rich energy wells. Herewith, not only the first steps in HBV assembly have been elucidated, but also the old prediction about assembly occurring via energy-rich protein contacts has been confirmed. These insights likely also apply to other virus particles and could be used in nanotechnological approaches.


Virus self-assembly proceeds through contact-rich energy minima

Pedro Buzón, Sourav Maity, Panagiotis Christodoulis, Monique J. Wiertsema, Steven Dunkelbarger, Christine Kim, Gijs J. L. Wuite, Adam Zlotnick, Wouter H. Roos

Science Advances Vol. 7, eabg0811 (2021)

Roos lab website:

Last modified:09 November 2021 4.02 p.m.
View this page in: Nederlands

More news

  • 13 October 2023

    Moniek Tromp appointed Captain of Science of the Top Sector Chemistry

    Prof. Moniek Tromp has been appointed Captain of Science of the Chemistry Top Sector by the Minister of Economic Affairs and Climate Policy. As from 1 July 2023, she succeeded Prof. Bert Weckhuysen from Utrecht University.

  • 12 September 2023

    Art in times of AI

    Leonardo Arriagada Beltran conducted his PhD research on the interface of computer-generated art and the constantly evolving field of Artificial Intelligence (AI). He will defend his Phd thesis on 21 September. His research offers valuable insights...

  • 28 August 2023

    Harish Vedantham and Casper van der Kooi nominated for 'Wetenschapstalent 2023'

    Harish Vedantham and Casper van der Kooi have been nominated by New Scientist for Wetenschapstalent 2023 (Science Talent 2023). This election is meant to give young scientists and their research a stage.