To study certain aspects of cells, researchers need the ability to take the innards out, manipulate them, and put them back. Options for this kind of work are limited, but researchers reporting May 10 in Cell Metabolism describe a "nanoblade" that can slice through a cell's membrane to insert mitochondria. The researchers have previously used this technology to transfer other materials between cells and hope to commercialize the nanoblade for wider use in bioengineering.
"As a new tool for cell engineering, to truly engineer cells for health purposes and research, I think this is very unique," says Mike Teitell, a pathologist and bioengineer at the University of California, Los Angeles (UCLA).
mtDNA sequence alterations are challenging to generate but desirable for basic studies and potential correction of mtDNA diseases. Here, we report a new method for transferring isolated mitochondria into somatic mammalian cells using a photothermal nanoblade, which bypasses endocytosis and cell fusion. The nanoblade rescued the pyrimidine auxotroph phenotype and respiration of ρ0 cells that lack mtDNA. Three stable isogenic nanoblade-rescued clones grown in uridine-free medium showed distinct bioenergetics profiles. Rescue lines 1 and 3 reestablished nucleus-encoded anapleurotic and catapleurotic enzyme gene expression patterns and had metabolite profiles similar to the parent cells from which the ρ0 recipient cells were derived. By contrast, rescue line 2 retained a ρ0 cell metabolic phenotype despite growth in uridine-free selection. The known influence of metabolite levels on cellular processes, including epigenome modifications and gene expression, suggests metabolite profiling can help assess the quality and function of mtDNA-modified cells.