Local sampling paints a global picture: Local concentration measurements sense direction in complex chemical gradients

Abstract

Detecting and interpreting extracellular spatial signals is essential for cellular orientation within complex environments, such as during directed cell migration or growth in multicellular development. Although the molecular understanding of how cells read spatial signals like chemical gradients is still lacking, recent work has revealed that stochastic processes at different temporal and spatial scales are at the core of this gradient sensing process in a wide range of eukaryotes. Fast biochemical reactions like those underlying GTPase activity dynamics form a functional module together with slower cell morphological changes driven by membrane remodelling. This biochemical-morphological module explores the environment by stochastic local concentration sampling to determine the source of the gradient signal, enabling efficient signal detection and interpretation before polarised growth or migration towards the gradient source is initiated. Here we review recent data describing local sampling and propose a model of local fast and slow feedback counteracted by gradient-dependent substrate limitation to be at the core of gradient sensing by local sampling.

Mating yeast cells use an intrinsic polarity site to assemble a pheromone-gradient tracking machine

“…Lew and colleagues (Dyer et al, 2013;McClure et al, 2015) and Peter and colleagues (Hegemann et al, 2015;Hegemann and Peter, 2017) have proposed stochastic local sampling models with the following common elements. (1) Polarity is not initially established at the CS in gradient-stimulated cells.…”

“…Moreover, recent studies suggest that polarity is not initially established at the CS. Rather, interacting polarity proteins collectively called the "polarity complex" (PC) were found to spontaneously assemble at random cortical positions in cells responding to artificial pheromone gradients (Dyer et al, 2013;Hegemann et al, 2015;McClure et al, 2015;Hegemann and Peter, 2017). The PC is then thought to move upgradient by "biased wandering" until it encounters sufficient Gβγ to fix its position at the CS.…”

Exploratory polarization facilitates mating partner selection inSaccharomyces cerevisiae

“…Spatial information about the pheromone landscape could be extracted by "global" or "local" sensing strategies (Hegemann and Peter, 2017;Kelley et al, 2015;Martin, 2019). In global sensing, cells compare the concentration of ligand-bound receptors around the cell surface to infer the direction of the pheromone source.…”

How yeast cells find their mates

“…Studies of cells treated with 93 uniform pheromone concentrations showed that when pheromone levels are high, the patch 94 stops moving (McClure, et al, 2015;Dyer, et al, 2013). In principle, this "exploratory 95 polarization" mechanism can explain error-correction by positing that movement of the patch 96 continues until cells sense high pheromone levels indicating that the patch is directed towards a 97 mating partner (Hegemann and Peter, 2017). 98 The extent to which yeast cells rely on global spatial sensing to orient the formation of a 99 polarity patch, versus exploratory polarization after the patch has formed, remains unclear.…”