Short-time diffusive fluxes over membrane receptors yields the direction of a signalling source

Abstract

An essential ability of many cell types is to detect stimuli in the form of shallow chemical gradients. Such cues may indicate the direction that new growth should occur, or the location of a mate. Amplification of these faint signals is due to intra-cellular mechanisms, while the cue itself is generated by the noisy arrival of signalling molecules to surface bound membrane receptors. We employ a new hybrid numerical-asymptotic technique coupling matched asymptotic analysis and numerical inverse Laplace transform to rapidly and accurately solve the parabolic exterior problem describing the dynamic diffusive fluxes to receptors. We observe that equilibration occurs on long timescales, potentially limiting the usefulness of steady-state quantities for localization at practical biological timescales. We demonstrate that directional information is encoded primarily in early arrivals to the receptors, while equilibrium quantities inform on source distance. We develop a new homogenization result showing that complex receptor configurations can be replaced by a uniform effective condition. In the extreme scenario where the cell adopts the angular direction of the first impact, we show this estimate to be surprisingly accurate.