Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins
Fig 6
An agent-based model showing the clustering of receptors in the presence of a high affinity crosslinker.
Agent-based modelling of the effect of changing the basal level of receptor phosphorylation and dimerisation, and the number of a high affinity crosslinker on receptor clustering. Unless stated, the parameter values and key are as described in Fig 4. (A) The effect of the number of high affinity crosslinkers on the proportion of receptor dimers for a receptor that is unable to dimerise (monomeric receptor) (i) representative runs at steady-state, the number of high affinity crosslinkers is shown in the upper right-hand corner (ii) number of receptors that are phosphorylated at steady-state (iii) number of receptor dimers (R = 2), trimers (R = 3), tetramers (R = 4) and higher order structures (R>4) at steady-state. Results are shown as mean + s.d. of 30 simulations at 3,000 ticks. (B) The effect of the number of high affinity crosslinker on clustering of a receptor with a basal level of dimerisation (10%) (i) the number of crosslinkers is shown in the upper right-hand corner, for further details see (A). (C) The effect of the basal level of receptor phosphorylation on clustering of receptors in the presence of a high affinity crosslinker (100 per box) (i) the rate of receptor phosphorylation per box is shown in ticks in the upper right-hand corner, for further details see (A). (D) The effect of the basal level of receptor dimerisation on clustering of receptors in the presence of a high affinity crosslinker (100 per box) (i) the rate of receptor dimerisation is shown in ticks in the upper right-hand corner, for further details see (A). (E) The effect of the number of high affinity crosslinkers on clustering of receptors in the presence of a high basal level of receptor dimerisation and phosphorylation. The rate of phosphorylation and degree of dimerisation are set to the highest values in (C) and (D) achieving ~80% and ~75% phosphorylation and dimerisation, respectively (i) The number of high affinity crosslinkers is shown in the upper right-hand corner, for further details see (A).