Structure, stability, and thermodynamics of lamellar DNA-lipid complexes
Structure, stability, and thermodynamics of lamellar DNA-lipid complexes
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DOI：
10.1016/s0006-3495(98)77503-4
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发表时间：
1998-07-01
影响因子：
3.4
通讯作者：
Ben-Shaul, A
中科院分区：
文献类型：
--
作者：
Harries, D;May, S;Ben-Shaul, A
我们建立了一个统计热力学模型，用于水溶液中DNA-阳离子脂质复合物的相演化，作为带电脂质与中性脂质和带电脂质与DNA之比的函数。通过最近的同步加速器x射线测量确定，这些复合物由嵌入在混合脂质双层层的层状堆叠水层中的平行DNA链组成，忽略了DNA和脂质双层的弹性变形，但包括了DNA引起的双层电荷密度的空间不均匀性。对相关非线性泊松-玻尔兹曼方程进行了数值求解，包括极化膜表面边界条件的自一致处理。对于大范围的脂质组成，相演化表现为三个区域的脂质与DNA电荷比，rho: 1)低rho时，复合物与多余的DNA共存，复合物中DNA-DNA间距d是恒定的；2)对于中间rho，包括等电点rho = 1，溶液中的所有脂质和DNA都被纳入络合物，其DNA间距离d随rho线性增加；3)对于高rho，复合物与过量脂质体共存（其脂质组成与复合物中的脂质体不同），其间距d与rho几乎无关，但不完全无关。这些结果可以用一个简单的电荷模型来理解，该模型反映了逆熵与dna间（rho < 1）和双层间（rho > 1）斥力之间的竞争。最后，将本文的方法和结论与前人的理论工作进行了比较，并与相关实验进行了比较。
We develop a statistical thermodynamic model for the phase evolution of DNA-cationic lipid complexes in aqueous solution, as a function of the ratios of charged to neutral lipid and charged lipid to DNA. The complexes consist of parallel strands of DNA intercalated in the water layers of lamellar stacks of mixed lipid bilayers, as determined by recent synchrotron x-ray measurements Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA-induced spatial inhomogeneities in the bilayer charge densities are included. The relevant nonlinear Poisson-Boltzmann equation is solved numerically, including self-consistent treatment of the boundary conditions at the polarized membrane surfaces. For a wide range of lipid compositions, the phase evolution is characterized by three regions of lipid to DNA charge ratio, rho: 1) for low rho, the complexes coexist with excess DNA, and the DNA-DNA spacing in the complex, d, is constant; 2) for intermediate rho, including the isoelectric point rho = 1, all of the lipid and DNA in solution is incorporated into the complex, whose inter-DNA distance d increases linearly with rho; and 3) for high rho, the complexes coexist with excess liposomes (whose lipid composition is different from that in the complex), and their spacing d is nearly, but not completely, independent of rho. These results can be understood in terms of a simple charging model that reflects the competition between counterion entropy and inter-DNA (rho < 1) and interbilayer (rho > 1) repulsions. Finally, our approach and conclusions are compared with theoretical work by others, and with relevant experiments.