Artificial Control of Cell Signaling Using a Photocleavable Cobalt(III)-Nitrosyl Complex

Abstract

Cells use gaseous molecules such as nitric oxide (NO) to transmit both intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Herein, it is shown that gasotransmitters use time-dependent dynamics to discriminate the endogenous and exogenous inputs. For a real-time stimulation of cell signaling, we synthesized a photo-cleavable metal-nitrosyl complex, [Co^III (MDAP)(NO)(CH₃ CN)]²⁺ (MDAP=N,N'-dimethyl-2,11-diaza[3,3](2,6)pyridinophane), which can stably deliver and selectively release NO with fine temporal resolution in the cytosol, and used this to study the extracellular signal-regulated kinases (ERKs), revealing how cells use both exogenous and endogenous NO to disentangle cellular responses. This technique can be to understand how diverse cellular signaling networks are dynamically interconnected and also to control drug delivery systems.

Keywords: cobalt(III)-nitrosyl complex; kinase translocation reporter; nitric oxide; photolysis; signal transduction.