New Super-Resolution Microscopy Shows The Inner Workings Of Cells As Never Before

For the first time, scientists can watch cells grow in four dimensions.


Let’s say you wanted to understand how a car engine works. A drawing of would give you a cursory overview of the machine. A 3-D image would add further depth and scope. But imagine if you could see the machine in motion and from the inside out. Then you’d not only be able to watch the valves moving up and down, but see the pistons firing inside those valves. This is the newest breakthrough that scientists have made in the field of microscopy, and it is revolutionizing their ability to understand the inner workings of cells.

Volume rendering of the amnioserosa and the encroaching epithelium during dorsal closure in a D. melanogaster embryo expressing GFP/DE-cadherin to highlight cell-cell junctions, over 840 time points at 8 sec intervals (cf., Fig. 6C). Bounding box, 86 x 80 x 31 μm.Betzig Lab, HHMI/Janelia Research Campus, Kiehart Lab, Duke University; 10/24/14 issue of the journal Science.

“If you really want to understand any kind of machine–and a cell is a biochemical machine–you need to see it in four dimensions,” says Eric Betzig, who won this year’s Nobel Prize in Chemistry and heads a bioimaging lab at the Janelia Research Campus of the Howard Hughes Medical Institute.

Specifically, Betzig’s team has perfected a new generation of Lattice Light Sheet Microscope, which uses light to illuminate the inner workings of a cell. It does this by optically “slicing” the cell, one very thin plane at a time, until the entire cell is photographed. It then repeats the process over and over, creating a real-time video depicting how the cell moves and grows. The breakthrough is about both precision and speed.

Imaging T. thermophila expressing GFP-scramblase in a single 2D plane at 3 ms intervals reveals the motions of individual cilia (cf., fig. S10). Magnified view is shown at right.Betzig Lab, HHMI/Janelia Research Campus, Janetopoulos Lab, University of the Life Sciences, Romero Lab, University of Minnesota; 10/24/14 issue of the journal Science. HHMI

“With old light sheets, you could see lots of detail about how embryos developed from an egg to a hatched larva,” says Betzig. “But the light sheet was too thick to look inside the cell.” Moreover, the longer you shone light on a cell, the greater risk of damaging it. “While light is a pretty gentle way of looking at living things, there are limits. The specimen can easily be cooked,” Betzig says. Remember cooking ants with your glasses as a kid? Betzig’s microscope avoids that outcome.

So what exactly does Betzig’s microscope allow scientists to see? The results–which can help scientists understand how T Cells fight infection, how cancer cells metastasize and how embryos develop–are forthcoming in the latest issue of Science. But you’ve got to see the cells in motion to understand the payoffs of this new super-resolution microscopy. The visuals may resemble alien blobs attempting to win at Dance, Dance Revolution, but they’re nothing less than the building blocks of life.

About the author

Jennifer Miller is the author of The Year of the Gadfly (Harcourt, 2012) and Inheriting The Holy Land (Ballantine, 2005). She's a regular contributor to Co.Create.