脂質與段鏈共聚高分子的混合薄膜及囊胞之研究探討

Hybrid Membranes and Vesicles of Lipids and Block Copolymers

黃鈞彥(Chun-Yen Huang)

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(2018年)

https://doi.org/10.6342/NTU201800823

摘要

混合脂質與高分子所形成的囊胞可以同時具有脂質囊胞和高分子囊胞的優點。於本研究中，利用耗散粒子動力學的模擬方法，探討脂質與雙段鏈共聚高分子形成混合薄膜的相行為。脂質的不飽和度與否以及脂質與高分子長度的差異性影響亦一併考慮。隨著脂質濃度超過某個臨界值以及不飽和度的增加，混合薄膜的相態將由均勻態(均勻分布)轉變至相分離(形成脂質雙層結構域)。研究發現促使相分離產生的驅動力，主要來自於脂質與高分子疏水段鏈間能量的弱不相容性。在單層小顆且相分離的混合囊胞中，依然能由脂質囊胞和高分子囊胞，以異質融合的方法形成。而異質融合和相分離的情形，無法以兩個不混溶的液滴解釋。當長度差異影響的重要度增加時，會延遲發生相分離，且在相分離之前，會出現單層的脂質筏狀物。脂質在混合薄膜中的流動性，與其物理狀態有關，且可以透過橫向擴散係數表示。在高分子為主的薄膜中，均勻態時，脂質擴散係數比較大，隨著脂質濃度的增加，脂質之間頻繁的接觸以及產生交疊，脂質的擴散係數隨之減少。
於本研究中，也利用耗散粒子動力學的模擬方法，探討脂質與三段鏈共聚高分子所形成混合薄膜的相行為。隨著脂質比例的增加，混合薄膜的相平衡態將由均勻態轉變至相分離。混合薄膜平衡的過程中，能藉由冷卻動力學控制脂質結構域的數量和大小，但是最終熱力學上，仍喜歡形成單一的脂質結構域。當脂質濃度較低時，脂質擴散係數會比較大。然而隨脂質結構域的形成，脂質擴散係數隨之下降，最後會接近純脂質擴散係數。當脂質與三段鏈高分子疏水鏈段長度差異不大時，脂質與三段鏈高分子會在兩物質邊界接觸上，作形狀的調整。然而差異太大時，雙層結構的脂質膜已經消失，並且出現脂質筏狀物。本研究亦發現U型三段鏈高分子很難與脂質混合，因此在混合薄膜中，U型三段鏈高分子會比I型三段鏈高分子與脂質混和時，更容易產生相分離。在理想的情形下，飽和脂質比例高於44%以上時，會產生相分離。然而不飽和脂質在所有的比例下，皆能形成均勻的混合薄膜。

關鍵字

脂質 ； 段鏈共聚高分子 ； 薄膜 ； 囊胞 ； 混合 ； 耗散粒子動力學 ； 分子模擬

並列摘要

Hybrid lipid/polymer vesicles can integrate benefits of liposomes and polymersomes. In this work, the phase behavior of hybrid membranes containing lipids and diblock copolymers is explored by dissipative particle dynamics simulations. The influences of lipid unsaturation and size mismatch between lipids and polymers are considered. The transition from the mixing state (homogenous distribution) to demixing state (formation of bilayered lipid-rich domains) is always observed as the lipid concentration exceeds a critical value, which increases with the degree of unsaturation. It is found that phase separation is driven by weak energy incompatibility between the hydrophobic segments of lipids and polymers. A small unilamellar vesicle in the demixing state can be developed by the heterogeneous fusion between polymersome and liposome. Such “heterogeneous fusion and demixing” cannot be explained by the encounter of two immiscible droplets. When the effect of size mismatch becomes significant, the occurrence of the demixing state is retarded, and monolayer lipid rafts emerge before phase separation. Lipid fluidity associated with the physical state of a hybrid membrane can be characterized by lateral lipid diffusivity. In the polymer-rich membrane, lateral lipid diffusivity is higher in the mixing state, but decreases generally with the lipid concentration due to lipid-lipid interactions and interdigitation.

The phase behavior of hybrid membranes containing lipids and triblock copolymers is also explored by dissipative particle dynamics simulations. It is found that the phase changes from a homogeneous distribution to phase separation as lipid concentration increases. The number and size of lipid-rich domains can be tuned by controlling the cooling kinetics with the process that hybrid membranes form. However, the development of a single lipid-rich domain is thermodynamically favorable eventually. When the lipid concentration is low, lipid diffusivity is high. As lipid-rich domain is formed, lipid diffusivity decreases toward that of a pure lipid membrane. When the membrane thickness of the hydrophobic parts of the triblocks and lipids are comparable, conformational adaption at lipid-triblock boundary is observed. As the size mismatch increases, lipid bilayer formation vanishes and lipid raft appear. We have also found that it is more difficult for U-shaped triblocks to be well-mixed with lipids and thus it is easier for the phase separation to take place for the U-shaped triblocks/lipids hybrid membranes than I-shaped triblocks/lipids ones. At the athermal condition, phase separation occurs when the lipid concentration is about 44% for saturated lipids. However, homogeneous phases are observed for unsaturated lipids for the entire composition range of the hybrid membranes.

並列關鍵字

lipid ； block copolymer ； membrane ； vesicle ； hybrid ； dissipative particle dynamic ； molecular simulation

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