Department of Biomedical Engineering, Ben Gurion University, Be'er Sheva 84105, Israel.
J Am Chem Soc. 2009 Mar 4;131(8):2875-81. doi: 10.1021/ja807278p.
We present a comprehensive set of simulations that elucidates several features of experimentally observed self-assembled structures in solutions of DNA and mixtures of neutral and cationic lipids. Our simulations are based on the Noguchi-Takasu implicit-solvent coarse-grained model of lipids as rigid trimer molecules [Noguchi, H.; Takasu, M. Phys. Rev. E 2001, 64, 041913.]. This model is extended in our work so that a certain fraction, varphi(c), of the lipids carries +1e charge and DNA molecules are introduced as uniformly charged rods. The simplified coarse-grained modeling approach provides a feasible way to study the long time-scale dynamics associated with the evolution of mesoscopically large complexes from initially disordered systems. Our simulations show that, depending on the rigidity parameter kappa(s) which governs the stiffness of the membranes, both lamellar and inverted hexagonal complexes are formed at intermediate charged lipid densities. Disordered structures are formed both when large amounts of neutral lipids (small varphi(c)) are introduced which leads to the "erosion" of the spatial order, as well as for large charge densities that result in membrane rupture. A novel phase, where DNA rods and cylindrical micelles form a two-dimensional square lattice analogous to the three-dimensional cubic NaCl-type structure, is observed in the large varphi(c) regime for very soft membrane material (kappa(s) = 0).
我们提出了一套全面的模拟，阐明了在 DNA 溶液和中性及阳离子脂质混合物中观察到的自组装结构的几个特征。我们的模拟基于 Noguchi-Takasu 刚性三聚物的无溶剂粗粒化脂质模型[ Noguchi, H.; Takasu, M. Phys. Rev. E 2001, 64, 041913. ]。在我们的工作中，对该模型进行了扩展，使得一部分脂质（ varphi(c) ）带有+1e 电荷，并且引入了带均匀电荷的 DNA 分子作为棒状分子。简化的粗粒化建模方法为研究与从初始无序系统演化而来的介观大复合物的长时间尺度动力学提供了一种可行的方法。我们的模拟表明，取决于控制膜刚度的刚性参数 kappa(s) ，在中间带电荷的脂质密度下，会形成层状和反六方复合物。当引入大量中性脂质（小 varphi(c) ）时会形成无序结构，这会导致空间有序的“侵蚀”，而当电荷密度较大时则会导致膜破裂。在非常软的膜材料（ kappa(s) = 0 ）下，对于大 varphi(c) 区域，会观察到一种新相，其中 DNA 棒和圆柱形胶束形成类似于三维立方 NaCl 型结构的二维正方形晶格。
