Influenza M2 Transmembrane Domain Senses Membrane Heterogeneity and Enhances Membrane Curvature

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• 作者：Chian Sing Ho ; Nawal K. Khadka ; Fengyu She ; Jianfeng Cai ; Jianjun Pan
• 刊名：Langmuir
• 出版年：2016
• 出版时间：July 5, 2016
• 年：2016
• 卷：32
• 期：26
• 页码：6730-6738
• 全文大小：598K
• 年卷期：0
• ISSN：1520-5827

文摘

Targeting host cell membranes by M2 of influenza A virus is important for virus invasion and replication. We study the transmembrane domain of M2 (M2TM) interacting with mica-supported planar bilayers and free-standing giant unilamellar vesicles (GUVs). Using solution atomic force microscopy (AFM), we show that the size of M2TM oligomers is dependent on lipid composition. The addition of M2TM to lipid bilayers containing liquid-ordered (Lo) and liquid-disordered (Ld) phases reveals that M2TM preferentially partitions into the Ld phase; phase-dependent partitioning results in a larger rigidity of the Ld phase. We next use fluorescence microscopy to study the effects of M2TM on phase-coexisting GUVs. In particular, M2TM is found to increase GUVs’ miscibility transition temperature T_mix. The augmented thermodynamic stability can be accounted for by considering an enhanced energy barrier of lipid mixing between coexisting phases. Our GUV study also shows that M2TM can elicit an array of vesicle shapes mimicking virus budding. M2TM enhanced membrane curvature is consistent with our AFM data, which show altered membrane rigidity and consequently line tension at domain edges. Together, our results highlight that in addition to conducting protons, M2TM can actively regulate membrane heterogeneity and augment membrane curvature.