Nanoscale FasL Organization on DNA Origami to Decipher Apoptosis Signal Activation in Cells

Cell signaling is initiated by characteristic protein patterns in the plasma membrane, but tools to decipher their molecular organization and activation are hitherto lacking. Among the well‐known signaling pattern is the death inducing signaling complex with a predicted hexagonal receptor architectu...

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Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2021-07, Vol.17 (26), p.e2101678-n/a
Main Authors: Berger, Ricarda M. L., Weck, Johann M., Kempe, Simon M., Hill, Oliver, Liedl, Tim, Rädler, Joachim O., Monzel, Cornelia, Heuer‐Jungemann, Amelie
Format: Article
Language:English
Subjects:
Apoptosis
cell apoptosis
Coupling (molecular)
Death
DNA origami
FasL/FasR
ligand‐receptor interactions
Nanotechnology
Receptors
Signaling
signaling complex
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Summary:Cell signaling is initiated by characteristic protein patterns in the plasma membrane, but tools to decipher their molecular organization and activation are hitherto lacking. Among the well‐known signaling pattern is the death inducing signaling complex with a predicted hexagonal receptor architecture. To probe this architecture, DNA origami‐based nanoagents with nanometer precise arrangements of the death receptor ligand FasL are introduced and presented to cells. Mimicking different receptor geometries, these nanoagents act as signaling platforms inducing fastest time‐to‐death kinetics for hexagonal FasL arrangements with 10 nm inter‐molecular spacing. Compared to naturally occurring soluble FasL, this trigger is faster and 100× more efficient. Nanoagents with different spacing, lower FasL number or higher coupling flexibility impede signaling. The results present DNA origami as versatile signaling scaffolds exhibiting unprecedented control over molecular number and geometry. They define molecular benchmarks in apoptosis signal initiation and constitute a new strategy to drive particular cell responses. DNA origami allows for nanometrically‐controlled arrangement of FasL, which are heavily involved in apoptosis signaling. FasL–DNA origami nanoagents displaying a hexagonal ligand arrangement with inter‐ligand distances of 10 nm exhibit a much faster and 100× higher signaling efficiency in HeLa cells than soluble FasL without pre‐arrangement.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.202101678