Oligomerization of peripheral membrane proteins provides tunable control of cell surface polarity

Asymmetric distributions of peripheral membrane proteins define cell polarity across all kingdoms of life. Non-linear positive feedback on membrane binding is essential to amplify and stabilize these asymmetries, but how specific molec-ular sources of non-linearity shape polarization dynamics remains poorly understood. Here we show that the ability to oligomer-ize, which is common to many peripheral membrane proteins, can play a profound role in shaping polarization dynamics in simple feedback circuits. We show that size-dependent binding avidity and mobility of membrane-bound oligomers endow po-larity circuits with several key properties. Size-dependent membrane binding avidity confers a form of positive feedback on the accumulation of oligomer subunits. Although insufficient by itself, this sharply reduces the amount of additional feedback required for spontaneous emergence and stable maintenance of polarized states. Size-dependent oligomer mobility makes symmetry breaking and stable polarity more robust with respect to variation in subunit diffusivities and cell sizes, and slows the approach to a final stable spatial distribution, allowing cells to "remember"polarity boundaries imposed by transient external cues. Together, these findings reveal how oligomerization of peripheral membrane proteins can provide powerful and highly tunable sources of non-linear feedback in biochemical circuits that govern cell surface polarity. Given its prevalence and wide-spread involvement in cell polarity, we speculate that self-oligomerization may have provided an accessible path to evolving sim-ple polarity circuits.