Signalling is of particular importance in immune cells, and upstream in the signalling pathway many membrane receptors are functional only as complexes, co-locating with particular lipid species. Work over the last 15 years has shown that plasma membrane lipid composition is close to a critical point of phase separation, with evidence that cells adapt their composition in ways that alter the proximity to this thermodynamical point. Macrophage cells are a key component of the innate immune system, responsive to infections, regulating the local state of inflammation. We investigate changes in the plasma membrane's proximity to the critical point, as a response to stimulation by various pro- and anti-inflammatory agents. Pro-inflammatory (IFN-, Kdo-LipidA, LPS) perturbations induce an increase in the transition temperature of the GMPVs; anti-inflammatory IL4 has the opposite effect. These changes recapitulate complex plasma membrane composition changes, and are consistent with lipid criticality playing a master regulatory role: being closer to critical conditions increases membrane protein activity.

Criticality of plasma membrane lipids reflects activation state of macrophage cells