A Ruthenium(II) Polypyridyl Complex Disrupts Actin Cytoskeleton Assembly and Blocks Cytokinesis

Angew Chem Weinheim Bergstr Ger. 2022 Jul 4;134(27):e202117449. doi: 10.1002/ange.202117449. Epub 2022 May 9.

Abstract
in English, German

The dinuclear RuII complex [(Ru(phen)2)2(tpphz)]4+ (phen=1,10-phenanthroline, tpphz=tetrapyridophenazine) "RuRuPhen" blocks the transformation of G-actin monomers to F-actin filaments with no disassembly of pre-formed F-actin. Molecular docking studies indicate multiple RuRuPhen molecules bind to the surface of G-actin but not the binding pockets of established actin polymerisation inhibitors. In cells, addition of RuRuPhen causes rapid disruption to actin stress fibre organisation, compromising actomyosin contractility and cell motility; due to this effect RuRuPhen interferes with late-stage cytokinesis. Immunofluorescent microscopy reveals that RuRuPhen causes cytokinetic abscission failure by interfering with endosomal sorting complexes required for transport (ESCRT) complex recruitment.

The dinuclear RuII complex [(Ru(phen)2)2(tpphz)]4+ binds to G‐actin monomers, preventing assembly into F‐actin. This inhibits actin fibre assemblies within live cells and causes disruption to late cytokinesis by interfering with the function of endosomal sorting complexes required for transport (ESCRT) during abscission. These results reveal new possibilities for metal complexes as biomedical tools and novel therapeutic leads.

Keywords: Actin; Cytokinesis; Cytoskeleton; Polypyridyl Complexes; Ruthenium.