Asymptotic analysis of particle cluster formation in the presence of anchoring sites

Abstract

The aggregation or clustering of proteins and other macromolecules plays an important role in the formation of large-scale molecular assemblies within cell membranes. Examples include lipid rafts and postsynaptic domains (PSDs). PSDs are rich in scaffolding proteins that transiently trap transmembrane neurotransmitter receptors, thus localizing them at specific spatial positions. Hence, PSDs play a key role in determining the strength of synaptic connections and their regulation during learning and memory. Recently, a 2D diffusion-mediated aggregation model of PSD formation has been developed in which the spatial locations of the clusters are determined by a set of fixed anchoring sites. The system is kept out of equilibrium by the recycling of particles between the cell membrane and interior. This results in a stationary distribution consisting of multiple clusters, whose average size can be determined using an effective mean-field description of the particle concentration around each anchored cluster. In this paper, we derive corrections to mean-field theory using asymptotic methods, assuming that the clusters are well separated and much smaller than the membrane surface. The analysis proceeds by matching inner solutions around each cluster with and an outer region where mean-field interactions occur. This generates an asymptotic expansion of the particle concentration that sums over all logarithmic terms involving the small parameter $ν=-1/\ln ε$, where $ε$ specifies the relative size of the clusters. This is then used to derive an expression for the radius of each cluster, which includes higher-order corrections to mean-field theory that depend on the positions of the clusters and the boundary of the domain. Finally, motivated by a recent study of light-activated protein oligomerization in cells, we develop the analogous theory for cluster formation in a 2D domain.