Ashkar Rana, Nagao Michihiro, Butler Paul D, Woodka Andrea C, Sen Mani K, Koga Tadanori
National Institute of Standards and Technology (NIST) Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland; Department of Material Science and Engineering, University of Maryland, College Park, Maryland.
National Institute of Standards and Technology (NIST) Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland; Center for Exploration of Energy and Matter, Indiana University, Bloomington, Indiana.
Biophys J. 2015 Jul 7;109(1):106-12. doi: 10.1016/j.bpj.2015.05.033.
Membrane thickness fluctuations have been associated with a variety of critical membrane phenomena, such as cellular exchange, pore formation, and protein binding, which are intimately related to cell functionality and effective pharmaceuticals. Therefore, understanding how these fluctuations are controlled can remarkably impact medical applications involving selective macromolecule binding and efficient cellular drug intake. Interestingly, previous reports on single-component bilayers show almost identical thickness fluctuation patterns for all investigated lipid tail-lengths, with similar temperature-independent membrane thickness fluctuation amplitude in the fluid phase and a rapid suppression of fluctuations upon transition to the gel phase. Presumably, in vivo functions require a tunability of these parameters, suggesting that more complex model systems are necessary. In this study, we explore lipid tail-length mismatch as a regulator for membrane fluctuations. Unilamellar vesicles of an equimolar mixture of dimyristoylphosphatidylcholine and distearoylphosphatidylcholine molecules, with different tail-lengths and melting transition temperatures, are used as a model system for this next level of complexity. Indeed, this binary system exhibits a significant response of membrane dynamics to thermal variations. The system also suggests a decoupling of the amplitude and the relaxation time of the membrane thickness fluctuations, implying a potential for independent control of these two key parameters.
膜厚度波动与多种关键的膜现象相关,如细胞交换、孔形成和蛋白质结合,这些现象与细胞功能和有效药物密切相关。因此,了解这些波动如何被控制会对涉及选择性大分子结合和高效细胞药物摄取的医学应用产生显著影响。有趣的是,先前关于单组分双层膜的报道显示,对于所有研究的脂质尾长,其厚度波动模式几乎相同,在液相中具有相似的与温度无关的膜厚度波动幅度,并且在转变为凝胶相时波动迅速受到抑制。据推测,体内功能需要这些参数具有可调性,这表明需要更复杂的模型系统。在本研究中,我们探索脂质尾长不匹配作为膜波动的调节剂。将具有不同尾长和熔化转变温度的二肉豆蔻酰磷脂酰胆碱和二硬脂酰磷脂酰胆碱分子的等摩尔混合物的单层囊泡用作这种更高复杂性水平的模型系统。确实,这个二元系统对热变化表现出显著的膜动力学响应。该系统还表明膜厚度波动的幅度和弛豫时间解耦,这意味着有可能独立控制这两个关键参数。