本研究利用耗散粒子動力學來研究由可離子化陽離子脂質形成的膜之穩定性，此脂質為脂質奈米顆粒的主要成分且能夠導致內體逃逸，因此考慮了三種具有不同尾部結構的可離子化模型脂質。內體酸化導致脂質電離，造成它們頭基之間的排斥範圍增加。當靜電排斥被建模為具有遠程截止距離的保守力時，膜和囊泡會失去結構完整性並隨著截止距離超過臨界值而形成孔洞，其值隨尾部結構變化。當庫侖排斥力被明確納入和加強時，完全電離的脂質膜會失去結構完整性，顯示出與增加截止距離的保守力對膜穩定性所觀察到的定性相似的效果。隨著帶電脂質分率的增加，部分電離膜也獲得了定性相似的結果。還研究了包含可離子化脂質和典型脂質的混合脂質膜之穩定性，其雙層結構的破壞發生在足夠高的帶電分率。膜不穩定性可歸因於隨著相互作用範圍的增加，因此可以由堆疊參數的降低且顯著偏離1來解釋。;The stability of membranes formed by ionizable cationic lipids, which constitute the primary components in lipid nanoparticles capable of endosomal escape, is explored using coarse-grained dissipative particle dynamics. Three types of ionizable model lipids with different tail structures are considered. Endosome acidification causes the ionization of lipids, leading to an increased repulsive range between their headgroups. When electrostatic repulsion is modeled as a conservative force with a long-range cutoff distance (r_(c,HH)), the membrane and vesicle experience a loss of structural integrity and develop holes as r_(c,HH) is beyond a critical value, which varies with the tail structure. When Coulombic repulsion is explicitly incorporated and intensified, a fully ionized lipid membrane undergoes a loss of structural integrity, displaying a qualitative similarity to the effect observed with the increase in r_(c,HH) on the membrane stability. Qualitatively similar results are obtained for partially ionized membranes as the fraction of charged lipids increases. The stability of a mixed lipid membrane containing both ionizable and conventional lipids is also investigated. The disruption of the bilayer structure occurs for sufficiently high charged fraction. The membrane instability can be attributed to the decrease in the packing parameter, which significantly deviates from unity as the interaction range increases.
