Performing cellular surgery with a laser-powered nanoblade

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). "We haven't run into anything so far, up to a few microns in size, that we can't deliver."

Teitell and Pei-Yu "Eric" Chiou, also a bioengineer at UCLA, first conceived the idea of a nanoblade several years ago to transfer a nucleus from one cell to another. However, they soon delved into the intersection of stem cell biology and energy metabolism, where the technology could be used to manipulate a cell's mitochondria. Studying the effects of mutations in the mitochondrial genome, which can cause debilitating or fatal diseases in humans, is tricky for a number of reasons.

The nanoblade apparatus consists of a microscope, laser, and titanium-coated micropipette to act as the "blade," operated using a joystick controller. When a laser pulse strikes the titanium, the metal heats up, vaporizing the surrounding water layers in the culture media and forming a bubble next to a cell. Within a microsecond, the bubble expands, generating a local force that punctures the cell membrane and creates a passageway several microns long that the "cargo"—in this case, mitochondria—can be pushed through. The cell then rapidly repairs the membrane defect.