The role of Notch ligand monomers and dimers in Notch receptor cis-inhibition and trans activation.

(A) The potential models governing cis-inhibition of Notch. The level of trans-ligand in sending cell is fixed whilst cis ligand levels in receiving cell vary as shown. (B) Notch activity in the receiving cell as a function of cis-ligand production rate for the different models shown in A. (C) Notch activity in the receiving cell as a function of cis-ligand dimerization rates for a high level of cis-ligand (the maximum production rate shown in B). (D) The potential models governing trans-activation of Notch. The production rate and dimerization rate of ligand in the receiving cell is fixed whilst trans ligand levels in sending cell vary as shown. (E) Notch activity in the receiving cell in response to increasing trans-ligand production rates for the different models shown in D. (F) Notch activity in the receiving cell in response to decreasing trans-ligand dimerization rates when the level of trans-ligand is high (the maximum production rate shown in E). (G) The potential roles of ligand monomer and ligand dimer governing Notch signaling in two identical cells. (H) Relative Notch activity in response to increasing Notch ligand production rates in two cells for the two cases shown in G. Notch activity is normalized against the maximum Notch activity. (I) In silico replication of published cis-inhibition dynamics [22]. In common with their experimental conditions [22], the initial state of ligand levels is high (with a production rate of 0), whilst Notch receptor levels are low.