Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK.
Alembic, Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.
J R Soc Interface. 2020 Feb;17(163):20190803. doi: 10.1098/rsif.2019.0803. Epub 2020 Feb 5.
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 thermodynamic point. Macrophage cells are a key component of the innate immune system, are responsive to infections and regulate 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 (interferon , Kdo 2-Lipid A, lipopolysaccharide) perturbations induce an increase in the transition temperature of giant plasma membrane vesicles; anti-inflammatory interleukin 4 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.
信号转导在免疫细胞中尤为重要，在信号通路的上游，许多膜受体只有作为复合物时才具有功能，与特定的脂质种类共定位。过去 15 年的研究表明，质膜脂质组成接近相分离的临界点，有证据表明，细胞通过改变接近热力学临界点的方式来适应其组成。巨噬细胞是先天免疫系统的关键组成部分，对感染有反应，并调节局部炎症状态。我们研究了质膜接近临界点的变化作为对各种促炎和抗炎剂刺激的反应。促炎（干扰素、Kdo2-脂 A、脂多糖）扰动诱导巨质膜囊泡的相变温度升高；抗炎白细胞介素 4 则有相反的效果。这些变化再现了复杂的质膜组成变化，并且与脂质临界性起着主要的调节作用一致：更接近临界条件会增加膜蛋白的活性。
