Computational Modeling to determine how variations in cell-cell contact length determines signal output

Cell-cell signaling and communication are fundamental to the existence of complex life. Among the various mechanisms by which cells communicate, the Notch signaling pathway is a prominent example. Synthetic Notch (synNotch) is a modified version of the Notch signaling pathway whereby direct contact between a signal-sending and a signal-receiving cell induces the transcription of a specific gene in the receiving cell. We focus on the synNotch implementation where its activation leads to the expression of Green Fluorescent Protein (GFP) in the receiving cell. Our previous in vivo observations showed that the synNotch GFP output increases with the length of contact between signal sending and receiving cells, with significant cell to cell variability in contact lengths. To understand and predict the impact of cell-cell contact length variations on synNotch signaling output, we developed a computational model for synNotch output based on the Gillespie Simulation Algorithm. By incorporating experimental measurements such as the signal output intensity and cell-cell contact lengths, our model aims to constrain parameters such as the synthesis and decay rates governing synNotch output in vivo.