Ultrafast laser method opens holes in cells to study mitochondrial DNA diseases

Researchers at the University of California Los Angeles (UCLA) have demonstrated a new ultrafast laser-driven method to conduct research on mitochondrial DNA diseases—a broad group of debilitating genetic disorders that can affect the brain, heart, and muscles. The method, which employs a technology developed by the research team, opens holes in the cell membrane and could pave the way for specific research on how and why these diseases occur, as well as point to pathways to develop treatments.

Related: Biophotonic tool can deliver large particles into 100,000 cells per minute

Mitochondria, small organelles that reside inside a cell's cytoplasm but outside the nucleus, convert food into energy and building blocks for cells in a process known as metabolism. Mutations in mitochondrial DNA (mtDNA), can cause devastating diseases that mainly affect tissues and cells with high-energy demands. One of the best-known mtDNA diseases is Leber's hereditary optic neuropathy, which can cause sudden and profound loss of central vision. Because mitochondria in humans are maternally inherited, mtDNA diseases can be passed from an unaffected mother to her children.

According to the researchers, mitochondria with healthy mtDNA could be delivered into cells with damaged mtDNA, which could dramatically reduce a disease's effects, or possibly eliminate it.

The process of transferring mitochondria between cells using the nanoblade technology. (Image credit: Alexander Patananan)

To begin to address these and other complex issues surrounding mtDNA alterations, the researchers—led by Dr. Michael Teitell, director of basic and translational research in the Jonsson Comprehensive Cancer Center at UCLA and the study's co-lead author, and Pei-Yu (Eric) Chiou, professor of mechanical and aerospace engineering at the UCLA Henry Samueli School of Engineering and Applied Science—collaborated on a new precision cutting tool. The tool, a "photothermal nanoblade," uses an ultrafast laser-induced cavitation bubble to open holes in the outer membrane of a cell. This enables pressurized delivery of desired contents—in this case, healthy mitochondria—into the cell cytoplasm. Chiou explains that their process keeps cells alive, as the nanoblade tool never enters the cell. "So, we can achieve a very high efficiency in the delivery of large-sized, slow-diffusing cargo, such as mitochondria," he says.

Osteosarcoma cells and mitochondria (green), with additional mitochondria (red) transferred via the nanoblade. (Image credit: Ting-Hsiang Wu)

Additionally, Chiou and Teitell are engineering an approach that incorporates the nanoblade into a high-throughput system that could deliver desired cargo, such as mitochondria, into as many as 100,000 cells per minute.

Full details of the work appear in the journal Cell Metabolism; for more information, please visit http://dx.doi.org/10.1016/j.cmet.2016.04.007.

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