Nanoscale protein clustering modulates the input-output response of cellular signalling pathways.

A key function of the plasma membrane is regulating signal transduction. Proteins involved in the transduction process play a signal-processing role; mapping an input (e.g. number of engaged receptors) to an output (e.g. level of downstream phosphorylation). In many cases, a digital mapping is desirable, i.e. that a cell activates or responds fully once a set input threshold is surpassed. It is hypothesised that the nanoscale organisation of proteins, such as their clustering, modulates this behaviour by altering the frequency of protein-protein interactions. Here, we develop a generalised simulator for dynamic molecular clustering built on agent-based modelling. We show that the clustering properties (e.g. size of clusters, percentage of monomers) tunes the cellular response. This work paves the way for designing potential therapeutic interventions that alter the nanoscale patterning of molecules on the cell surface to influence cell behaviour.