To disentangle the elusive lipid–protein interactions in T-cell activation, we investigate how externally imposed variations in mobility of key membrane proteins (T-cell receptor [TCR], kinase Lck, and phosphatase CD45) affect the local lipid order and protein colocalisation. Using spectral imaging with polarity-sensitive membrane probes in model membranes and live Jurkat T cells, we find that partial immobilisation of proteins (including TCR) by aggregation or ligand binding changes their preference towards a more ordered lipid environment, which can recruit Lck. Our data suggest that the cellular membrane is poised to modulate the frequency of protein encounters upon alterations of their mobility, for example in ligand binding, which offers new mechanistic insight into the involvement of lipid-mediated interactions in membrane-hosted signalling events.

中文翻译：

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膜蛋白的聚集和迁移与 T 细胞质膜中的局部脂质顺序相互作用

为了解开 T 细胞活化中难以捉摸的脂质-蛋白质相互作用，我们研究了关键膜蛋白（T 细胞受体 [TCR]、激酶 Lck 和磷酸酶 CD45）迁移率的外部强加变化如何影响局部脂质顺序和蛋白质共定位. 在模型膜和活 Jurkat T 细胞中使用具有极性敏感膜探针的光谱成像，我们发现通过聚集或配体结合对蛋白质（包括 TCR）的部分固定改变了它们对更有序的脂质环境的偏好，这可以招募 Lck。我们的数据表明，细胞膜准备好在改变它们的流动性时调节蛋白质遇到的频率，例如在配体结合中，