Title: Receptor length and enzyme size together has crowding effects on tethered signaling processes.
Abstract:
Much of cell signaling occurs near the cell membrane, involving reactions between tethered enzymes. So far, most in vitro and in silico studies have considered tethered reactions without the significance of enzyme crowding, even though in vivo estimates expect crowding effects to be significant. In particular, a recent surface plasmon resonance experiment found that the binding rate of the cytoplasmic enzyme SHP-1 to the surface receptor PD-1 decreases as the density of the system increases. We hypothesize this result is due to crowding effects. To quantify the significance of crowding effects on signaling biochemistry, we develop a computational method that efficiently (on the scale of $\sim O(n^{1.23})$) simulates tethered reactions with crowding effects, by iterating between a Gillespie-style algorithm for reactions and a Metropolis-style algorithm for computing entropic and steric effects. We find that while protein density has little effect on dephosphorylation rates, tether length and enzyme size has a significant crowding effect on dephosphorylation. This work offers an efficient and insightful method to studying tethered signaling reactions, and considers specific tether properties that can be tuned in biomedical engineering applications.