Our MD data indicate that the critical amino acid ASPβ127 will be protonated on the majority of integrins as long as the extracellular pH is less than the predicted pKa of this residue within the integrin (6.692); therefore, we chose pH 6.5 for these long-timescale cell-level experiments.
It is important to note that each movie is much shorter than the characteristic timescale of cell migration.
Instead, they evolve on each time-step, reflecting the assumption that vessel adaptation occurs on the same timescale as cell movement and proliferation.
As the timescale of cell growth (hours) is much slower than the timescale of the cdr2p dynamics (minutes, Figure 2 figure supplement 4), we assumed that the molecular system is, at any given time, effectively in steady state.
Response delay constraints are likely to be less important for developmental networks, since they control irreversible processes on the timescale of cell-cycles.
Again, there is an overshoot because E and T change slowly on the timescale of one cell generation.
Only after E starts being produced and T degraded, which occurs on the timescale of one cell generation, does the increase/decrease of s slow down.
However, if the downshift is so large that the positive feedback is switched off, then the response is relatively slow, on the timescale of one cell generation (see Fig. 1).
Unlike macroscopic valve designs, the protein allows differential ion flows in the pumping and resting states that are tuned to match the physiological timescales of the cell, thus creating a "kinetic" valve.
The importance of extra-splenic killing and recirculation could be tested with non-destructive sampling of the blood immediately after transfer (that is, over the short timescale during which cells are migrating into the spleen) to test that the ratio of pulsed to unpulsed targets in blood is preserved.
Using different fluorescence fluctuation approaches, we established that paxillin-EGFP is dynamic on many timescales within the cell, ranging from milliseconds to seconds.
