How the biomimetic assembly of membrane receptors into multivalent domains is regulated by a small ligand

Abstract

[eng] In living cells, communication requires the action of membrane receptors that are activated following verysmall environmental changes. A binary all-or-nothing behavior follows, making the organism extremelyefficient at responding to specific stimuli. Using a minimal system composed of lipid vesicles, chemicalmodels of a membrane receptor and their ligands, we show that bio-mimetic ON/OFF assembly of highavidity, multivalent domains is triggered by small temperature changes. Moreover, the intensity of the ONsignal at the onset of the switch is modulated by the presence of small, weakly binding divalent ligands,reminiscent of the action of primary messengers in biological systems. Based on the analysis ofspectroscopic data, we develop a mathematical model that rigorously describes the temperaturedependentswitching of the membrane receptor assembly and ligand binding. From this we derive anequation that predicts the intensity of the modulation of the ON signal by the ligand-messenger asa function of the pairwise binding parameters, the number of binding sites that it features and theconcentration. The behavior of our system, and the model derived, highlight the usefulness of weaklybinding ligands in the regulation of membrane receptors and the pitfalls inherent to their bindingpromiscuity, such as non-specific binding to the membrane. Our model, and the equations derived fromit, offer a valuable tool for the study of membrane receptors in both biological and biomimetic settings.The latter can be exploited to program membrane receptor avidity on sensing vesicles, createhierarchical protocell tissues or develop highly specific drug delivery vehicles.<br />