The question of how the chemical composition of a protein—the amino acid sequence—determines its 3D structure has been one of the biggest challenges in biophysics for more than half a century. This knowledge about the so-called “folding” of proteins is in great demand, as it contributes significantly to the understanding of various diseases and their treatment, among other things. For these reasons, Google’s DeepMind research team has developed AlphaFold, an artificial intelligence that predicts 3D structures.

A team consisting of researchers from Johannes Gutenberg University Mainz (JGU) and the University of California, Los Angeles, has now taken a closer look at these structures and examined them with respect to knots. We know knots primarily from shoelaces and cables, but they also occur on the nanoscale in our cells. Knotted proteins can not only be used to assess the quality of structure predictions but also raise important questions about folding mechanisms and the evolution of proteins.

A team of scientists in the Physical Intelligence Department at the Max Planck Institute for Intelligent Systems have combined robotics with biology by equipping E. coli bacteria with artificial components to construct biohybrid microrobots. First, as can be seen in Figure 1, the team attached several nanoliposomes to each bacterium. On their outer circle, these spherical-shaped carriers enclose a material (ICG, green particles) that melts when illuminated by near infrared light. Further towards the middle, inside the aqueous core, the liposomes encapsulate water soluble chemotherapeutic drug molecules (DOX).

The second component the researchers attached to the bacterium is magnetic nanoparticles. When exposed to a magnetic field, the iron oxide particles serve as an on-top booster to this already highly motile microorganism. In this way, it is easier to control the swimming of bacteria —an improved design toward an in vivo application. Meanwhile, the rope binding the liposomes and magnetic particles to the bacterium is a very stable and hard to break streptavidin and biotin complex, which was developed a few years prior and reported in a Nature article, and comes in useful when constructing biohybrid microrobots.

E. coli bacteria are fast and versatile swimmers that can navigate through material ranging from liquids to highly viscous tissues. But that is not all, they also have highly advanced sensing capabilities. Bacteria are drawn to chemical gradients such as low oxygen levels or high acidity—both prevalent near tumor tissue. Treating cancer by injecting bacteria in proximity is known as bacteria mediated tumor therapy. The microorganisms flow to where the tumor is located, grow there and in this way activate the immune system of patients. Bacteria mediated tumor therapy has been a therapeutic approach for more than a century.