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@ARTICLE{Mauker:282305,
author = {Mauker, Philipp and Beckmann, Daniela and Kitowski, Annabel
and Heise, Constanze and Wientjens, Chantal and Davidson,
Andrew J and Wanderoy, Simone and Fabre, Gabin and Harbauer,
Angelika B and Wood, Will and Wilhelm, Christoph and
Thorn-Seshold, Julia and Misgeld, Thomas and
Kerschensteiner, Martin and Thorn-Seshold, Oliver},
title = {{F}luorogenic {C}hemical {P}robes for {W}ash-free {I}maging
of {C}ell {M}embrane {D}amage in {F}erroptosis, {N}ecrosis,
and {A}xon {I}njury.},
journal = {Journal of the American Chemical Society},
volume = {146},
number = {16},
issn = {0002-7863},
address = {Washington, DC},
publisher = {ACS Publications},
reportid = {DZNE-2025-01275},
pages = {11072 - 11082},
year = {2024},
abstract = {Selectively labeling cells with damaged membranes is needed
not only for identifying dead cells in culture, but also for
imaging membrane barrier dysfunction in pathologies in vivo.
Most membrane permeability stains are permanently colored or
fluorescent dyes that need washing to remove their
non-uptaken extracellular background and reach good image
contrast. Others are DNA-binding environment-dependent
fluorophores, which lack design modularity, have potential
toxicity, and can only detect permeabilization of cell
volumes containing a nucleus (i.e., cannot delineate damaged
volumes in vivo nor image non-nucleated cell types or
compartments). Here, we develop modular fluorogenic probes
that reveal the whole cytosolic volume of damaged cells,
with near-zero background fluorescence so that no washing is
needed. We identify a specific disulfonated fluorogenic
probe type that only enters cells with damaged membranes,
then is enzymatically activated and marks them. The esterase
probe MDG1 is a reliable tool to reveal live cells that have
been permeabilized by biological, biochemical, or physical
membrane damage, and it can be used in multicolor
microscopy. We confirm the modularity of this approach by
also adapting it for improved hydrolytic stability, as the
redox probe MDG2. We conclude by showing the unique
performance of MDG probes in revealing axonal membrane
damage (which DNA fluorogens cannot achieve) and in
discriminating damage on a cell-by-cell basis in embryos in
vivo. The MDG design thus provides powerful modular tools
for wash-free in vivo imaging of membrane damage, and
indicates how designs may be adapted for selective delivery
of drug cargoes to these damaged cells: offering an outlook
from selective diagnosis toward therapy of
membrane-compromised cells in disease.},
cin = {AG Misgeld},
ddc = {540},
cid = {I:(DE-2719)1110000-4},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38592946},
doi = {10.1021/jacs.3c07662},
url = {https://pub.dzne.de/record/282305},
}