Evidence for non-chemical, non-electrical intercellular signaling in intestinal epithelial cells

Synchrony between mechanically separated biological systems is well known. We posed the question: can cells induce synchronous behavior in neighboring cells which are mechanically separated and which cannot communicate via chemical or electrical mechanisms. Caco-2 cell cultures were divided into three groups. “Inducer” cells were exposed to H2O2. “Detector” cells were placed in separate containers near the inducer cells but were not exposed to H2O2. Control cells were exposed to fresh media and were kept in a distant laboratory area. Samples were measured for total protein concentration, NFκB activation and structural changes, 10, 30 and 60 min after exposure respectively. Exposing inducer cells to H2O2 resulted in a significant reduction in total protein content (− 50%), an increase in nuclear NFκB activation (+ 38%), and structural damage (56%) compared to controls. There was a similar reduction in total protein content (− 48%), increase in the nuclear fraction of NFκB (+ 35%) and structural damage (25%) in detector cells. These findings provide evidence in support of a non-chemical, non-electrical communication. This signaling system possibly plays a role in synchronous, stimulus-appropriate cell responses to noxious stimuli and may explain a number of cellular behaviors that are hard to explain based only on conventional cell signaling systems.