Notch and Delta stick briefly but tightly.

Cell type specification by Notch (N) in one cell and Delta (Dl) in another must happen quickly, before morphogenesis further changes the cellular landscape. On page 1217 Ahimou et al. find that the adhesion force between N and Dl peaks and drops in just 10 min, symptomatic of a peak and drop in intercellular signaling. Pulling on Dl can accelerate this process.

To measure the in vivo adhesion force between N and Dl, Ahimou et al. attached a Drosophila cell expressing one or the other protein to a cantilever tip of an atomic force microscope (AFM) and placed cells expressing the other protein in a culture dish. When they brought the AFM tip with the cell near those in the culture dish, they found that, unlike many biologically active molecular pairs, there was no attractive force detected between N and Dl. After pushing the cells together, however, it took up to 14 nN of force to detach them, which is 50 to 250 times the force it takes to dislodge streptavidin from biotin.

Binding of Dl to N is known to cause cleavage of the intracellular, signaling domain of N by presenilin. This proceeded at the highest rate when the adhesion forces between the proteins was high. The force required to separate N and Dl expressing cells dropped off after presenilin cleavage and fell to nearly zero in just 10 min, suggesting that the proteins complete their signaling reaction quickly.

Both the brief and rapid signaling, as well as the increased signaling rate induced by Dl pulling, fits with the role of the N-Dl signaling during development, when there are morphogenetic movements and rapid changes in cell identity. Previous work has identified numerous factors that regulate N-Dl signaling. The team plans to use their new AFM system to decipher the biochemical and biophysical impact of these regulators.