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There is just one issue, however – they are incredibly small, less than a few square microns in area, so manipulating them has been beyond the reach of even the most advanced research departments.
That could change thanks to new work at ETH Zurich in Switzerland, where researchers have successfully transplanted the tiny components between living cells. With important implications for our understanding of intracellular processes and the evolution of life, the ground-breaking work was enabled by a tiny ‘nanosyringe’ developed for the task.
Tiny pipette
Under an electron microscope, a needle-like tip can be seen protruding from the end of a ‘cantilever’ on a nanoscale pipette. With a hollow tip to suck in the cellular component, it is capable of working in the femtolitre-to-picolitre range (one-thousand trillionth to one-trillionth of a litre).
“The technology combines atomic force microscopy, optical microscopy and nanofluidics to achieve force and volume control with realtime inspection. We developed dedicated probes that allow minimally invasive entry into cells and optimised fluid flow to extract specific organelles,” wrote the researchers in a paper published in PLOS Biology.
The syringe was designed by Dr Tomaso Zambelli, who combined the high-precision approach of an atomic force microscope with the volumetric dispensing of nanoscale pipettes under optical inspection, providing the forces and volume control needed to manipulate single cells. The syringe was built layer by layer in a micro-fabrication process at SmartTip, a probing specialist based at the University of Twente in the Netherlands. The outside of the cantilever was built from silicon nitride, to which a 1-micron layer of polysilicon was added to fabricate the internal channel. Another layer of silicon nitride was added, before chemical etching removed the polysilicon.
“You remain with a hollow space confined between the two layers, like a sandwich,” said Zambelli.
In the mitochondria transplant work, the position of the cylindrical nanosyringe was controlled by laser light from a converted atomic force microscope. A pressure regulator adjusted the flow, allowing scientists to transfer incredibly small volumes of fluid in the femtolitre range during transplants of the organelles.
The researchers pierced the cell membrane and sucked up the spherical mitochondria, before piercing the membrane of a different cell and pumping the mitochondria out of the nanosyringe and into the recipient cell.
Understanding evolution
The transplanted mitochondria had a survival rate of more than 80%, said the researchers. In most cases, the injected mitochondria began to fuse with the filamentous network of the new cell 20 minutes after transplantation.
Both the donor and acceptor cells also survived the “minimally invasive” procedure, said Christoph Gäbelein, lead author of the paper.
The research will have applications in various areas in future, said the team. Led by Dr Julia Vorholt at the ETH Zurich Institute of Microbiology, they said the technique could be used to rejuvenate stem cells, which exhibit a decline in metabolic activity as they age. The team’s current aim is to increase understanding of the processes that control how different cell compartments co-operate, and to unravel how endosymbiosis develops – a process in which cells join with others to form interdependent communities, which played a major role in the evolutionary development of life on Earth.
With such precise and reliable extraction of the components that underpin key biological processes, the nanosyringe is likely to see wider application in future.
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