New Microscope Gives Unprecedented High-Res View Inside Human Cells

"All my life I’ve dreamed of seeing this."

Any kid who ever paged through The Magic School Bus at their school’s book fair or watched the animated show on TV in the Nineties definitely fantasized about diving into the cells of the human body, just like Miss Frizzle and the gang did in the classic episode where Arnold turned orange. Amazingly, a new microscopy technique described in the journal Science on Friday makes those deep dives possible, and there are gorgeous videos to prove it.

In the paper, a team of scientists describes a 3D imaging technique that allows them to peer into the hidden world of a living cell without destroying it, which is the downside of other available techniques. The combination of two processes makes this high-resolution 3D imaging possible: lattice light-sheet microscopy (LLSM), which images one slice of the cell at a time, and adaptive optics (AO), which corrects for any blurriness. The technique has already enabled researchers to observe processes that they’ve only ever been able to see indirectly. “I work on understanding how cells ‘eat’ using machinery based on vesicular carriers, and all my life I’ve dreamed of seeing this in a live organism,” Tomas Kirchhausen, Ph.D., a professor of cell biology at Harvard Medical School and one of the paper’s authors, said in a statement on Thursday. “We have finally achieved this.”

The new technique allows scientists to view processes like this cancer cell (green) invading a blood vessel (purple).

Liu et al/ Science

While the end result looks crisp and effortless, it actually requires a lot of problem-solving to get a glimpse into a cell. The structure of a cell makes it hard for anything to get in or out without the cell’s permission, and all the other cells and tissues surrounding it makes it hard to get a clear view, as these structures can scramble the light passing through. By parsing the cells with slices of laser light and then correcting for any obstruction with the same AO technique astronomers use to correct blurriness in observations of stars, the scientists have come up with a microscopy technique that looks like an artistic rendering.

Since developing their technique, the team has used it to image cellular scenarios that would wow even Miss Frizzle. The microscope has been used to peer inside blood vessels being invaded by cancer cells and capture white blood cells while they chomp down on sugars inside a fish eyeball. In one stunning video, the team uses the technique to “explode” the cells of a zebrafish eye, allowing the viewer to step into the spaces between the millions of cells that make up the organ.

“It’s like ‘Star Trek.’ It’s the age of exploration again,” Srigokul Upadhyayula, Ph.D., an instructor in pediatrics at Boston Children’s Hospital and one of the co-lead authors, said in a statement. “We don’t even know what questions to ask yet because we’ve never even seen some of these biologies at this level of detail.”

The study’s authors say AO-LLSM could generate hypotheses about cell biology that they haven’t even imagined before. Since this level of clarity is so unprecedented, only time will tell how it changes the state of cell biology research.

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