Researchers have succeeded in controlling the size of a hollow protein container just a handful of nanometres in diameter. The work “Programmable polymorphism of a virus-like particle” was recently published in Communications Materials.
Human technology has often relied on using nature as the starting point but improving on it. Think of a bird versus an aeroplane. At the nanoscale this is also true: Viruses are masters at carrying cargo (their own genetic material) packed inside a tiny protein container which they deliver to the inside of cells. The features of these containers though are somewhat constrained by the evolutionary history of the virus. This is a problem if we want to co-opt them for carrying cargoes such as medicines which require more space to carry a dose that will provide clinical benefit. From the point of view of viral evolution however, if your natural cargo is small then why evolve to be larger than needed which is energy wasteful.
In the new work, researchers used a common tool in biotechnology, based on a bacteriophage (a virus that infects bacteria) called MS2. They modified the protein shell (or capsid, made from multiple copies of a protein that can be arranged in two slightly different forms) by adding short amino acid sequences into a loop on the outside of the capsid. ‘What we found is that the amino acid sequences added affected the rate at which the proteins change from one form to the other’, explains Jonathan Heddle, the leader of the project and corresponding author or the work. ‘In turn this controls the relative amounts of each form which affects how the proteins are able to fit together to make the capsid and ultimately, its size and shape’, he added. Specifically, the researchers were able to shift the capsid to make larger forms, something which the researchers hope may lead to designer capsids whose dimensions are tuned to match their purpose.
The work was carried out at Bionanoscience and Biochemistry Lab at the JU Małopolska Centre of Biotechnology in collaboration with Professor Reidun Twarock’s group at the Department of Mathematics, University of York