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Histochem Cell Biol. 2014 Jul;142(1):91-101. doi: 10.1007/s00418-014-1195-0. Epub 2014 Feb 12.

Quantitative single-molecule localization microscopy combined with rule-based modeling reveals ligand-induced TNF-R1 reorganization toward higher-order oligomers.

Author information

1
Institute for Physical and Theoretical Chemistry, Johann-Wolfgang-Goethe-University Frankfurt, Frankfurt am Main, Germany.

Abstract

We report on the assembly of tumor necrosis factor receptor 1 (TNF-R1) prior to ligand activation and its ligand-induced reorganization at the cell membrane. We apply single-molecule localization microscopy to obtain quantitative information on receptor cluster sizes and copy numbers. Our data suggest a dimeric pre-assembly of TNF-R1, as well as receptor reorganization toward higher oligomeric states with stable populations comprising three to six TNF-R1. Our experimental results directly serve as input parameters for computational modeling of the ligand-receptor interaction. Simulations corroborate the experimental finding of higher-order oligomeric states. This work is a first demonstration how quantitative, super-resolution and advanced microscopy can be used for systems biology approaches at the single-molecule and single-cell level.

PMID:
24519400
DOI:
10.1007/s00418-014-1195-0
[Indexed for MEDLINE]

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