A cell’s life: The movie
A sampling of biological systems captured by the new imaging technique.
Tsung-Li Liu et al.
Cells and cellular organelles don’t operate in isolation or on glass microscope slides. Rather, they function in a complex environment that conditions what they do. Thus, to fully understand cellular and subcellular processes, a biologist needs to observe cells in their native habitat.
Light-sheet fluorescence microscopy (LSFM) is one promising and gentle approach for imaging in vivo (see the Quick Study by Abhishek Kumar, Daniel A. Colón-Ramos, and Hari Shroff, Physics Today, July 2015, page 58 ). With LSFM, a specimen is illuminated with a micron-thick sheet of laser light; structures that have been tagged with fluorescent dyes then glow and reveal their positions. As the light plane is scanned in the normal direction, a three-dimensional micrograph emerges. Now a multi-institutional team led by Eric Betzig (Howard Hughes Medical Institute’s Janelia Research Campus) has combined LSFM with adaptive optics to generate high-resolution movies depicting cellular and even subcellular processes in zebrafish embryos and other biological systems.
The need for adaptive optics arises because the index of refraction in the complex cellular environment varies dramatically in space. As a result, wavefronts passing through the sample suffer an unknown distortion. In their approach to image correction, Betzig and colleagues induce points in the sample to fluoresce—that is, they create a cellular biologist’s version of the astronomer’s guide stars—and measure the distortion in their stars’ wavefronts. Armed with that information, they bounce the fluorescence light emitted by the entire sample off a mirror that is deformed to compensate for the average guide-star distortion. An independent, analogous procedure corrects for the aberrations created as the illuminating laser-light sheet passes through the sample. The result is an LSFM micrograph with greatly improved resolution.
Tsung-Li Liu et al.
The movie, from which the figure above was extracted, indicates the quality of the combined imaging technique. The green sphere in the figure is a cancer cell, about 10 µm in diameter, that was implanted in a zebrafish. Note the thin tendrils that adhere to the zebrafish’s blood vessel (magenta) as the cancer cell rolls along the vessel wall. Other portions of the movie show the cell in a blockier shape, crawling along the wall and, creepiest of all, extruding material that allows it to cross through the vessel wall into the surrounding tissue. (T.-L. Liu et al., Science 360, eaaq1392, 2018 .)
Movie 10 – Cancer cell migration in a zebrafish xenograft model from HHMI NEWS on Vimeo .