title: Correlated light microscopy and electron microscopy.
abstract: Understanding where, when, and how biomolecules (inter)act is crucial to uncover fundamental mechanisms in cell biology. Recent developments in fluorescence light microscopy (FLM) allow protein imaging in living cells and at the near molecular level. However, fluorescence microscopy only reveals selected biomolecules or organelles but not the (ultra)structural context, as can be examined by electron microscopy (EM). LM and EM of the same cells, so-called correlative (or correlated) light and electron microscopy (CLEM), allow examining rare or dynamic events first by LM, and subsequently by EM. Here, we review progress in CLEM, with focus on matching the areas between different microscopic modalities. Moreover, we introduce a method that includes a virtual overlay and automated large-scale imaging, allowing to switch between most microscopes. Ongoing developments will revolutionize and standardize CLEM in the near future, which thus holds great promise to become a routine technique in cell biology.
authors.affiliation: Department of Cell Biology, University Medical Center Groningen (UMCG), University of Groningen, A. Deusinglaan 1, Bldg 3215, room 749, 9713 AV Groningen, The Netherlands.
authors.forename: Klaas A
authors.initials: KA
authors.lastname: Sjollema
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schnell
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kuipers
authors.forename: Ruby
authors.initials: R
authors.lastname: Kalicharan
authors.forename: Ben N G
authors.initials: BN
authors.lastname: Giepmans
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008867:Microtomy; D059010:Single-Cell Analysis; D013194:Staining and Labeling
chemical_list: D005456:Fluorescent Dyes