Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins
Fig 4
Parameter values and symbols used for agent-based modelling.
(A) The symbols used to represent species in the agent-based model Figures are shown. The number of receptors (R), crosslinkers (S) and divalent ligands (LL) per box is 100 unless stated. (B) The default values for on-rates and off-rates are shown in ticks (arbitrary unit of time), with one tick corresponding to the ‘go’ function within each run. These represent the probability of a reaction to occur out of 100 runs. These are arbitrary values selected for illustrative purposes. They have been chosen to give a low basal level of dimerisation and phosphorylation to correspond to a resting platelet. Two sets of values have been chosen to reflect a moderate and high affinity crosslinker in regulating cluster formation; the latter takes into account that the affinity of a ‘moderate’ affinity crosslinker can be increased by its co-localisation in the membrane as is the case for the majority of SH2-domain containing proteins. A ‘low’ value was selected for the affinity of the ligand to reflect the affinity of individual epitopes in endogenous ligands for platelet glycoprotein receptors, noting that this can be increased by avidity. The selection of a relatively low value enables illustration of how variables can combine to drive clustering. The rate of movement of receptors is constant at 1 patch per tick patch is an arbitrary unit of area (there are 441 patches per box). The default values give rise to to a basal value of 10% receptor dimerisation and 10% receptor phosphorylation in the absence of crosslinker. The crosslinker can only bind to a phosphorylated receptor: the probability of each epitope of the crosslinker to bind to a phosphorylated receptor is shown as an average frequency per 100 ticks. Assuming that both epitopes are occupied, the ‘moderate’ affinity crosslinker will remain bound to two receptors for 16 out of 100 ticks on average. The ‘high’ affinity crosslinker will remain bound to the receptor for 81 out of 100 ticks, on average. The probability of each epitope of the divalent ligand to attach to a receptor upon collision was set to 20 out of 100 ticks and to dissociate to 20 out of 100 ticks. Assuming that both epitopes of the divalent ligand are bound at the same time, a fully occupied divalent ligand will remain bound to both receptors for an average 4 out of 100 ticks.