Versatile nanospheres

Researchers build artificial cellular compartments as molecular workshops.

Modified Cryo-EM image of genetically expressed molecular workshops inside living cells. (Image: P. Erdmann / Max-Planck-Institute of Biochemistry)
Modified Cryo-EM image of genetically expressed molecular workshops inside living cells. (Image: P. Erdmann / Max-Planck-Institute of Biochemistry)

How to make the cells more efficient by installing new capabilities without interfering their metabolic processes? Now, scientists at the Technical University of Munich (TUM) along with the Helmholtz Zentrum München have altered mammalian cells and created artificial compartments in which sequestered reactions could take place.

Scientists did this by introducing into human cells the genetic information for producing bacterial proteins, so-called encapsulants, which self-assemble into nanospheres. This method allowed the scientists to detect the cells deep in the tissue and also their manipulation with magnetic fields.

Felix Sigmund, the study’s first author said, “One of the system’s crucial advantages is that we can genetically control which proteins, for example, fluorescent proteins or enzymes, are encapsulated in the interior of the nanospheres. We can thus spatially separate processes and give the cells new properties.”

The fascinating properties of these nanospheres include,

  • They are non-toxic to the cell and enzymatic reactions can take place inside them without disturbing the cell’s metabolic processes.
  • They can take in iron atoms and process them in such a way that they remain inside the nanospheres without disrupting the cell’s processes. This sequestered iron biomineralization makes the particles and also the cells magnetic.

Scientists additionally showed that the nanospheres are also visible in high-resolution cryo-electron microscopy. This feature makes them useful as gene reporters that can directly mark the cell identity or cell status in electron microscopy, similar to the commonly used fluorescent proteins in light microscopy.

Prof. Gil Westmeyer, Professor of Molecular Imaging at TUM said, “To render cells visible and controllable remotely by making them magnetic is one of our long-term research goals. The iron-incorporating nano-compartments are helping us to take a big step towards this goal.”

“One possible future use of the artificial cellular compartments is, for example, cell immunotherapies, where immune cells are genetically modified in such a way that they can selectively destroy a patient’s cancer cells. With the new nano-compartments inside the manipulated cells, the cells could in the future be possibly located easier via non-invasive imaging methods.”

“Using the modularly equipped nano-compartments, we might also be able to give the genetically modified cells new metabolic pathways to make them more efficient and robust. There are of course many obstacles that have to be overcome in preclinical models first, but the ability to genetically control modular reaction vessels in mammalian cells could be very helpful for these approaches.”

The study is published in the journal Nature Communications.