Decision making through self-assembly on membranes

In living systems, self-assembly of macromolecular complexes is persistently occurring. The process of self-assembly itself can play a functional role in sensing and decision making. Inspired by key steps in endocytosis, we show how spontaneous molecular self-assembly on a two-dimensional substrate can act as a tunable and robust switch for detecting receptors at physiological concentrations. In this way, the assembly process produces a switch-like response that is sensitive to receptor density and membrane adhesiveness, helping ‘decide’ when receptors reach a critical threshold for uptake. Unlike the more familiar signalling pathways that sense and respond to receptor activation using irreversible, energy-consuming reactions, this assembly-based mechanism can work passively. We derive analytical expressions for critical receptor densities that switch on nucleation and growth of assemblies, in close agreement with equilibrium stochastic reaction-diffusion simulations. Finally, we discuss how our results can inform self-assembly during other spatial localization problems, and as it couples to mechanical work.