A research group at Massachusetts Institute of Technology (MA, USA) has engineered hypermagnetic protein nanoparticles that can be produced within target cells
Engineers from the Massachusetts Institute of Technology (MA, USA) have designed magnetic protein nanoparticles that can be used to track cells or to monitor interactions within cells. The particles are an enhanced version of a naturally occurring weakly magnetic protein called ferritin.
“Ferritin, which is as close as biology has given us to a naturally magnetic protein nanoparticle, is really not that magnetic. That’s what this paper is addressing,” commented Alan Jasanoff, senior author of the paper. “We used the tools of protein engineering to try to boost the magnetic characteristics of this protein.”
The new ‘hypermagnetic’ protein nanoparticles can be produced within cells, allowing the cells to be imaged or sorted using magnetic techniques. This eliminates the need to tag cells with synthetic particles and allows the particles to sense other molecules inside cells.
Previous research has already yielded synthetic magnetic particles for imaging or cell tracking, but it can be difficult to deliver these particles into target cells.
In the new study, Jasanoff and colleagues set out to create magnetic particles that are genetically encoded by delivering a gene for a magnetic protein into the target cells, prompting them to start producing the protein on their own.
“Rather than actually making a nanoparticle in the lab and attaching it to cells or injecting it into cells, all we have to do is introduce a gene that encodes this protein,” explained Alan Jasanoff.
The researchers started by using ferritin, which carries a supply of iron atoms that every cell needs as components of metabolic enzymes. In hope of creating a more magnetic version of ferritin, the researchers created about 10 million variants and tested them in yeast cells.
After repeated rounds of screening, the researchers used one of the most promising candidates to create a magnetic sensor consisting of enhanced ferritin modified with a protein tag that binds with another protein called streptavidin.
Because the engineered ferritins are genetically encoded, they can be manufactured within cells that are programmed to make them respond only under certain circumstances, when the cell receives an external signal, when it divides, or when it differentiates into another type of cell for example.
Researchers could track this activity using magnetic resonance imaging potentially allowing them to observe communication between neurons, activation of immune cells, or stem cell differentiation.
Such sensors could also be used to monitor the effectiveness of stem cell therapies. “As stem cell therapies are developed, it’s going to be necessary to have noninvasive tools that enable you to measure them,” added Jasanoff. “Without this kind of monitoring, it would be difficult to determine what effect the treatment is having, or why it might not be working.”
The team is currently working on adapting the magnetic sensors to work in mammalian cells.
Sources: http://news.mit.edu/2015/engineers-design-nanoparticles-magnetic-cell-sensors-1102; Matsumoto Y, Chen R, Anikeeva P, Jasanoff A. Engineering intracellular biomineralization and biosensing by a magnetic protein. Nature Communications, doi: 10.1038/ncomms9721 (2015) (Epub ahead of print)