Thermodynamics of cationic lipid binding to DNA and DNA condensation: Roles of electrostatics and hydrophobicity
Thermodynamics of cationic lipid binding to DNA and DNA condensation: Roles of electrostatics and hydrophobicity
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DOI：
10.1021/ja0124055
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发表时间：
2002-06-26
影响因子：
15
通讯作者：
Bloomfield, VA
中科院分区：
文献类型：
--
作者：
Matulis, D;Rouzina, I;Bloomfield, VA
用等温滴定量热法研究了烷基铵与DNA的结合。实验数据作为烷基链长、盐浓度、DNA浓度和温度的函数，提供了导致DNA缩合的脂质-DNA结合反应的详细热力学描述。脂质结合、反离子置换和DNA缩合是高度合作的过程，由较大的熵增加驱动，而在室温下受到相对较小的吸热热的反对。较大的负热容量变化表明，脂肪族尾部之间的疏水相互作用做出了贡献。由两个因素--离子和疏水相互作用--控制的脂质-DNA结合的近似模型与实验数据是一致的。确定了化学基团对结合能量学的贡献，并可用于预测其他脂类与DNA结合的能量学，应用加和性原理可以区分静电和疏水对吉布斯自由能、焓、熵和热容的贡献。研究了脂类与两个、三个和四个脂肪族尾巴的结合，并与单尾脂类结合进行了比较。在结构上，该模型认为脂类阳离子头部和脂族尾部均匀分布，并躺在DNA表面，没有形成胶束。
Alkylammonium binding to DNA was studied by isothermal titration calorimetry. Experimental data, obtained as functions of alkyl chain length, salt concentration, DNA concentration, and temperature, provided a detailed thermodynamic description of lipid-DNA binding reactions leading to DNA condensation. Lipid binding, counterion displacement, and DNA condensation were highly cooperative processes, driven by a large increase in entropy and opposed by a relatively small endothermic enthalpy at room temperature. Large negative heat capacity change indicated a contribution from hydrophobic interactions between aliphatic tails. An approximation of lipid-DNA binding as dominated by two factors-ionic and hydrophobic interactions-yielded a model that was consistent with experimental data. Chemical group contributions to the energetics of binding were determined and could be used to predict energetics of other lipid binding to DNA, Electrostatic and hydrophobic contributions to Gibbs free energy, enthalpy, entropy, and heat capacity could be distinguished by applying additivity principles. Binding of lipids with two, three, and four aliphatic tails was investigated and compared to single-tailed lipid binding. Structurally, the model suggests that lipid cationic headgroups and aliphatic tails distribute evenly and lay down on DNA surface without the formation of micelles.