Observing the Cell in Its Native State: Imaging Subcellular Dynamics in Multicellular Organisms
By
Tsung-Li Liu,
Srigokul Upadhyayula,
Daniel E. Milkie,
Ved Singh,
Kai Wang,
Ian A. Swinburne,
Kishore R. Mosaliganti,
Zach M. Collins,
T. W. Hiscock,
Jamien Shea,
Abraham Q. Kohrman,
Taylor N Medwig,
Daphne Dambournet,
Ryan Forster,
Brian Cunniff,
Yuan Ruan,
Hanako Yashiro,
Steffen Scholpp,
E. M. Meyerowitz,
Dirk Hockemeyer,
David G. Drubin,
Benjamin L Martin,
David Q. Matus,
Minoru Koyama,
Sean G. Megason,
Tom Kirchhausen,
Eric Betzig
Posted 08 Jan 2018
bioRxiv DOI: 10.1101/243352
(published DOI: 10.1126/science.aaq1392)
True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution without inducing undue stress on either. We combined lattice light sheet microscopy with two-channel adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages, and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.
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