Morphology matters in immune cell chemotaxis: membrane asymmetry affects amplification

Abstract

A key mediator of eukaryotic chemotaxis is the asymmetric accumulation of phosphatidylinositol-3,4,5-triphosphate (PIP3) on the cell membrane. Recent work has focused on understanding how a shallow external gradient of chemoattractant leads to an amplified internal gradient of PIP3. In this paper we dissect what fraction of this amplification is derived biochemically by the signal transduction network and how much arises entirely from the effects of cell morphology. Here we identify and formalize the role of morphology in signal detection and demonstrate its effects through simulation and experiments. Our key result is that an asymmetric distribution of membrane accounts for approximately one-half of the measured amplification from ligand concentration to PIP3 production. We also show that the underlying biochemical network behaves as a linear amplifier in the micropipette assay.