Single-cell directional sensing at ultra-low chemoattractant concentrations from extreme first-passage events

TL;DR

This study reveals that single cells can rapidly and accurately determine the direction of a chemoattractant source at ultra-low concentrations by analyzing early receptor binding events, even with few observations.

Contribution

The paper introduces a theoretical framework for understanding how early receptor binding events inform cellular directional sensing at low chemoattractant concentrations.

Findings

Early binding events provide more information about source direction.

Cells can localize sources accurately with few receptor binding events.

Analytic expressions for receptor binding distributions are derived.

Abstract

We investigate single-cell directional sensing from diffusing chemoattractant signals released by a localized source. We focus on the low-concentration regime in which receptor activity is discrete and cellular decisions are made on timescales far shorter than those required for steady-state concentration profiles or receptor occupancy to emerge. We derive analytic expressions for the joint distribution of receptor binding times and binding locations, conditional on the position of the source. We show that early binding events carry disproportionately more information about source directionality than later arrivals. Motivated by this observation, we propose and analyze several source-localization estimates that exploit early receptor binding statistics. Our results demonstrate that, even with a small number of binding events, cells possess sufficient information to rapidly and accurately infer the directionality of a diffusing chemoattractant source.