School of Materials Science and Engineering , Nanyang Technological University , 50 Nanyang Avenue , 639798 Singapore.
School of Chemical Engineering , Sungkyunkwan University , Suwon 16419 , Republic of Korea.
Langmuir. 2019 Mar 5;35(9):3568-3575. doi: 10.1021/acs.langmuir.9b00244. Epub 2019 Feb 15.
Monoglycerides are esterified adducts of fatty acid and glycerol molecules that disrupt phospholipid membranes, leading to a wide range of biological functions such as antimicrobial activity. Among monoglycerides, glycerol monolaurate (GML) exhibits particularly high antimicrobial activity, although enzymatic hydrolysis of its ester group can diminish potency. Consequently, there have been efforts to identify more chemically stable versions of GML, most notably its alkylglycerol ether equivalent called dodecylglycerol (DDG). However, despite high structural similarity, biological studies indicate that DDG and GML are not functionally equivalent and it has been speculated that the two compounds might have different interaction profiles with phospholipid membranes. To address this outstanding question, herein, we employed supported lipid bilayer (SLB) platforms to experimentally characterize the interactions of DDG with phospholipid membranes. Quartz crystal microbalance-dissipation experiments identified that DDG causes concentration-dependent membrane morphological changes in SLBs and the overall extent of membrane remodeling events was greater than that caused by GML. In addition, time-lapsed fluorescence microscopy imaging experiments revealed that DDG causes extensive membrane tubulation that is distinct from how GML induces membrane budding. We discuss how differences in the head group properties of DDG and GML contribute to distinct membrane interaction profiles, offering insight into how the molecular design of DDG not only improves chemical stability but also enhances membrane-disruptive activity.
单甘油脂是脂肪酸和甘油分子的酯化加合物，会破坏磷脂膜，从而产生广泛的生物学功能，如抗菌活性。在单甘油脂中，甘油单月桂酸酯（GML）表现出特别高的抗菌活性，尽管其酯基的酶水解会降低其效力。因此，人们一直在努力寻找更具化学稳定性的 GML 版本，最著名的是其烷基甘油醚等效物，称为十二烷基甘油（DDG）。然而，尽管结构高度相似，但生物学研究表明，DDG 和 GML 在功能上并不等效，有人推测这两种化合物可能与磷脂膜的相互作用模式不同。为了解决这个悬而未决的问题，在此，我们使用支持脂质双层（SLB）平台来实验表征 DDG 与磷脂膜的相互作用。石英晶体微天平耗散实验表明，DDG 会导致 SLB 中浓度依赖性的膜形态变化，并且膜重塑事件的总体程度大于 GML 引起的程度。此外，延时荧光显微镜成像实验表明，DDG 会引起广泛的膜管化，这与 GML 诱导的膜出芽方式不同。我们讨论了 DDG 和 GML 的头基性质差异如何导致不同的膜相互作用模式，深入了解了 DDG 的分子设计不仅提高了化学稳定性，还增强了膜破坏活性的原因。
