脂質與三段鏈共聚高分子混合膜的對稱與非對稱形成

Formation of Symmetric and Asymmetric Hybrid Membranes of Lipids and Triblock Copolymers

蔡祥詰(Hsiang-Chi Tsai)

指導教授 ： 諶玉真

國立臺灣大學/工學院/化學工程學研究所/碩士(2020年)

https://doi.org/10.6342/NTU202001404

摘要

本論文是透過耗散粒子動力學研究脂質與三段鏈(ABA)共聚高分子的混合膜，其中三段鏈高分子在膜中的型態通常分為I型(bridge-shape)和U型(loop-shape)。當U型態的高分子在膜的上下小葉(leaflets)的比例不同時，則稱為不對稱的膜。本研究發現當疏水鏈段(B)與脂質的頭基親和性較好的情況下(章節3.1)，膜中高分子I型的比例會因此下降。除此之外，U型高分子的構型也發生了改變，從原本的三維線圈狀結構轉成二維平面的構型，與實驗得到的結果一致。另外，當I型態在熱力學上不能穩定存在的時候，I型態的比例幾乎為零，也就是只有U型態在膜中，此時不對稱膜結構可以長時間穩定維持。當三段鏈高分子中兩段親水鏈段(A)長度不同，且不同長度的親水鏈段在膜的上下分布不均時，不對稱膜會自發性地出現並且能夠長期穩定。
此外，當疏水鏈段(B)與脂質的尾基親和性較好且排斥脂質頭基的情況下(章節3.2)，發現高分子親水鏈段的長度也會造成膜的型態影響。當高分子親水鏈段較短時，U型態的平衡比例與初始膜的結構無關，只受疏水鏈段長度的影響；而當高分子是親水鏈段較長時，U型態的比例因為動力學上能量的阻礙，導致其比例不會變化，維持與初始膜的結構一致。由此結果得知，當高分子擁有短親水鏈段時，只能形成對稱的膜，而穩定不對稱的膜能夠由長親水鏈段所組成。

關鍵字

脂質/三段鏈高分子混合膜 ； 只有U型態的混合膜 ； 不對稱膜 ； 增強穩定性 ； 高分子與脂質間親和性 ； 耗散粒子動力學

並列摘要

Hybrid membranes of lipid bilayers co-assembled with ABA triblock copolymers are studied by dissipative particle dynamics. The copolymer conformations in the membranes can be generally characterized as bridge- and loop-shapes. The hybrid membrane is designated asymmetric as the fractions of the loop-shape copolymers in the upper and lower leaflets are different. Our simulation results (Sec. 3.1) demonstrate that the presence of the bridge-shape copolymers (f_B^*) is inhibited as the hydrophobic B-block becomes more compatible with the lipid head. Moreover, the conformation of the loop-shape copolymer changes significantly, from a three-dimensional random-coil conformation to a two-dimensional flattened conformation which is consistent with the experimental findings. It was also found that a loop conformation-only, asymmetric hybrid membrane can stably sustain for a very long time as the bridge-shape copolymers are thermodynamically unstable within a membrane, i.e. f_B^*≈0. For membranes with asymmetric triblock copolymers, Ax1ByAx2 where x_1 is short and x_2 is long, asymmetric membranes can spontaneously emerge and stably exist over a long time provided that the Ax1 and Ax2 are inequitably distributed in the upper and lower leaflets.
In addition, when the hydrophobic segment is compatible with lipid tail and repels lipid head (Sec. 3.2), the long-time fraction of loop-conformation (f_L) of AxByAx copolymers in the membrane depends significantly on the hydrophilic block length (x). As x is small, an equilibrium f_L^* always results irrespective of the initial conformation distribution and its value depends on the hydrophobic block length (y). For large x, f_L tends to be time-invariant because polymers are kinetically trapped in their initial structures. Our findings reveal that only symmetric hybrid membranes are formed for small x, while membranes with stable asymmetric leaflets can be constructed with large x. The effects of block lengths on the polymer conformations, such as transverse and lateral spans (d^⊥ and d^(||)) of bridge- and loop-conformations, are discussed as well.

並列關鍵字

lipid/triblock hybrid membrane ； loop conformation-only hybrid membrane ； asymmetric membrane ； enhanced stability ； polymer-lipid compatability ； dissipative particle dynamics

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