Hakobyan Davit, Heuer Andreas
Theory of Complex Systems, University of Muenster, Muenster, Germany.
PLoS One. 2014 Feb 3;9(2):e87369. doi: 10.1371/journal.pone.0087369. eCollection 2014.
The lipid mixture of DPPC (saturated lipid)/DUPC (unsaturated lipid)/CHOL (cholesterol) is studied with respect to its ability to form liquid-ordered and liquid-disordered phases. We employ coarse-grained simulations with MARTINI force field. All three components are systematically modified in order to explore the relevant molecular properties, leading to phase separation. Specifically, we show that the DPPC/DUPC/CHOL system unmixes due to enthalpic DPPC-DPPC and DPPC-CHOL interactions. The phase separation remains unchanged, except for the formation of a gel phase at long times after decreasing the conformational degrees of freedom of the unsaturated DUPC. In contrast, the phase separation can be suppressed by softening the DPPC chains. In an attempt to mimic the ordering and unmixing effect of CHOL the latter is replaced by a stiff and shortened DPPC-like lipid. One still observes phase separation, suggesting that it is mainly the rigid and planar structure of CHOL which is important for raft formation. Addition of an extra bead to the head of CHOL has no notable impact on the phase separation of the system, supporting the irrelevance of the Umbrella model for the phase separation. Reduction of the conformational entropy of CHOL by stiffening its last bead results in a significant increase of the order of the DPPC/CHOL domain. This suggests that the conformational entropy of CHOL is important to prohibit the gelation process. The interleaflet interactions as mediated by the terminal molecular groups seem to have a strong impact on the possibility of a subsequent gelation process after phase separation.
研究了二棕榈酰磷脂酰胆碱（饱和脂质）/二油酰磷脂酰胆碱（不饱和脂质）/胆固醇（CHOL）的脂质混合物形成液相有序相和液相无序相的能力。我们采用了具有MARTINI力场的粗粒度模拟。对所有三种成分进行了系统修饰，以探索相关分子性质，从而导致相分离。具体而言，我们表明，由于焓驱动的二棕榈酰磷脂酰胆碱-二棕榈酰磷脂酰胆碱和二棕榈酰磷脂酰胆碱-胆固醇相互作用，二棕榈酰磷脂酰胆碱/二油酰磷脂酰胆碱/胆固醇体系发生了相分离。除了在降低不饱和二油酰磷脂酰胆碱的构象自由度后长时间形成凝胶相外，相分离保持不变。相反，通过软化二棕榈酰磷脂酰胆碱链可以抑制相分离。为了模拟胆固醇的有序化和相分离效应，用一种刚性且缩短的类似二棕榈酰磷脂酰胆碱的脂质取代了胆固醇。仍然观察到相分离，这表明主要是胆固醇的刚性和平面结构对筏的形成很重要。在胆固醇头部添加一个额外的珠子对体系的相分离没有显著影响，这支持了伞形模型与相分离无关的观点。通过硬化胆固醇的最后一个珠子来降低其构象熵，会导致二棕榈酰磷脂酰胆碱/胆固醇结构域的有序度显著增加。这表明胆固醇的构象熵对于阻止凝胶化过程很重要。由末端分子基团介导的层间相互作用似乎对相分离后随后的凝胶化过程的可能性有很大影响。
