Department of Chemistry and Biochemistry , University of North Carolina Wilmington , Wilmington , North Carolina 28403 , United States.
Langmuir. 2018 Aug 21;34(33):9798-9809. doi: 10.1021/acs.langmuir.8b01774. Epub 2018 Aug 8.
The excess heat capacity (Δ C ) of mixtures of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Chol) is examined in detail in large unilamellar vesicles (LUVs), both experimentally, using differential scanning calorimetry (DSC), and theoretically, using a three-state Ising model. The model postulates that DPPC can access three conformational states: gel, liquid-disordered (L), and liquid-ordered (L). The L state, however, is only available if coupled with interaction with an adjacent Chol. Δ C was calculated using Monte Carlo simulations on a lattice and compared to experiment. The DSC results in LUVs are compared with literature data on multilamellar vesicles (MLVs). The enthalpy change of the complete phase transition from gel to L is identical in LUVs and MLVs, and the melting temperatures ( T) are similar. However, the DSC curves in LUVs are significantly broader, and the maxima of Δ C are accordingly smaller. The parameters in the Ising model were chosen to match the DSC curves in LUVs and the nearest-neighbor recognition (NNR) data. The model reproduces the NNR data very well. It also reproduces the phase transition in DPPC, the freezing point depression induced by Chol, and the broad component of Δ C in DPPC/Chol LUVs. However, there is a sharp component, between 5 and 15 mol % Chol, that the model does not reproduce. The broad component of Δ C becomes dominant as Chol concentration increases, indicating that it involves melting of the L phase. Because the simulations reproduce this component, the conclusions regarding the nature of the phase transition at high Chol concentrations and the structure of the L phase are important: there is no true phase separation in DPPC/Chol LUVs. There are large domains of gel and L phase coexisting below T of DPPC, but above T the three states of DPPC are mixed with Chol, although clusters persist.
我们详细研究了在大单层囊泡（LUV）中，二棕榈酰磷脂酰胆碱（DPPC）和胆固醇（Chol）混合物的过剩热容（ΔC），实验上使用差示扫描量热法（DSC），理论上使用三态伊辛模型。该模型假定 DPPC 可以进入三种构象状态：凝胶、无序液体（L）和有序液体（L）。然而，只有在与相邻 Chol 相互作用的情况下，L 态才是可用的。通过在晶格上进行蒙特卡罗模拟计算了ΔC，并与实验进行了比较。LUV 中的 DSC 结果与多层囊泡（MLV）上的文献数据进行了比较。LUV 中完整的凝胶到 L 相相变的焓变与 MLV 中的相同，且熔融温度（T）相似。然而，LUV 中的 DSC 曲线明显更宽，ΔC 的最大值相应更小。伊辛模型中的参数选择是为了匹配 LUV 中的 DSC 曲线和最近邻识别（NNR）数据。该模型很好地再现了 NNR 数据。它还再现了 DPPC 中的相转变、Chol 引起的冰点降低以及 DPPC/Chol LUV 中ΔC 的宽峰成分。然而，模型没有再现 5 到 15mol%Chol 之间的一个陡峭成分。随着 Chol 浓度的增加，ΔC 的宽峰成分变得占主导地位，表明它涉及 L 相的熔融。由于模拟再现了这一成分，因此关于高 Chol 浓度下相转变的性质和 L 相结构的结论是重要的：在 DPPC/Chol LUV 中没有真正的相分离。在 DPPC 的 T 以下，存在凝胶和 L 相共存的大区域，但在 T 以上，DPPC 的三种状态与 Chol 混合，尽管仍存在簇。
