Extracting cytoplasmic material such as proteins, RNA, and mitochondria often relies on cell lysis using detergents or enzymes, which destroy the cells. Ultrasound and other sophisticated physical disruption methods need to be carefully tuned to avoid damaging biomolecules, potentially rendering them too time-consuming.
Delivering material into cells presents further challenges. Lipid-based carriers are limited to small molecules, viral vectors are costly, and microinjection techniques are difficult to scale. To date, no approach allows for controlled and efficient cytoplasmic transfer without compromising cell viability, according to researchers from Waseda University in Japan.
The team published a study “A Nanotube Injector for Cytoplasmic Transfer and Enhanced Mitochondrial Function” in Small Science that reports the development of a nanotube membrane-based injector—a platform that combines nanomaterials and fluid physics to directly transfer cytoplasmic contents between cell populations. The system consists of a thin gold membrane with vertically aligned nanotubes mounted on a glass tube. When this membrane is carefully pressed against cultured cells, the nanotubes penetrate the phospholipid bilayer of the living cells without causing significant damage. By adjusting the internal air pressure of the glass tube, the researchers can “suck up” cytoplasmic material from the source cells, hold it as the tube is repositioned over the target cell culture, and gently flush it into this new population using microliters of a buffer solution.
Through several experiments using fluorescent dyes and protein assays, the researchers say they confirmed that cytoplasmic contents could be extracted in a pressure-dependent manner. They also found that careful selection of nanotube diameter, nanotube density, and applied pressure was key to minimizing cellular damage. Notably, under optimized conditions, cell viability hovered around 95%, with a cytoplasmic transfer efficiency of well over 90%, note the scientists.
To further test the capabilities of their platform, the team investigated whether it could transfer intact mitochondria. To this end, they labeled mitochondria in donor cells with a fluorescent tag and observed them in the recipient cells via confocal microscopy. They found that dozens of mitochondria could be reliably delivered per cell.
Most importantly, according to Takeo Miyake, PhD, team leader, these mitochondria remained functional, as evidenced by markedly higher levels of adenosine triphosphate (ATP) produced in recipient cells compared to controls.
“This technology establishes a new paradigm for cell manipulation—transforming cells not by genetic modification but by reconstructing intracellular composition itself,” explains Miyake, adding that such controlled cytoplasmic engineering, enabled by the proposed nanotube injector, could support the development of next-generation cell therapies, improved disease models, and more precise drug screening platforms.
“Directly transferring healthy mitochondria or cytoplasmic components into target cells is particularly relevant for regenerative medicine, where therapeutic cells often suffer from reduced metabolic activity or functional heterogeneity after isolation and expansion,” highlights Miyake, “By restoring or augmenting mitochondrial function without genetic modification, the technology offers a new strategy to improve cell quality prior to transplantation.”
Overall, this innovative system paves the way for a new level of control in cell biology research, as well as bioengineering and biomedical applications, points out the research team.
