Reversible Control of cAMP Activity in Living Cells by Visible Light

Cyclic adenosine monophosphate (cAMP) is one of the most prominent molecules involved in intracellular signaling. As a second messenger, it regulates a plethora of biochemical processes that are essential to keep a cell alive and orchestrates physiological responses to external stimuli. Ever since its discovery, great efforts have been made to elucidate all the molecular mechanisms involved in cAMP-mediated signaling cascades. However, experimental evidence suggests that cAMP-mediated signal transduction is much more complex than previously assumed. For new insights, it is crucial to study the real-time dynamics and reversibility of the cAMP-related signaling mechanisms, which often remain disguised by classic pharmacological assays or modulators of cAMP signaling. By chemically attaching a photoswitchable moiety to cAMP, we got control over the biological activity of the molecule through visible light of different wavelengths. Combined with label-free electric cell-substrate impedance sensing (ECIS), the dynamic response of living cells treated with photochromic cAMP has been monitored in real-time while the cAMP-mediated signaling cascade is reversibly switched on and off by visible light with high temporal resolution.