Diacylglycerols (DAGs) are bioactive lipids that are ubiquitously present at low concentrations in cellular membranes. Upon the activation of lipid remodeling enzymes such as phospholipase C and phosphatidic acid phosphatase, DAG concentration increases, leading to a disruption of the lamellar phase of lipid membranes. To investigate the structural origin of these phenomena, here we develop a coarse-grained model for DAGs that is able to correctly reproduce its physicochemical properties, including interfacial tension and flip-flop rate. We find that even at low concentrations a nonnegligible percentage of DAG molecules occupies the interleaflet space. At high concentrations, DAG molecules undergo a phase-separation process from lamellar lipids, segregating in DAG-only blisters and effectively reducing the DAG surface pool available to peripheral enzymes. Our results allow for a better understanding of the role of DAGs in cellular membranes and provide a new tool for the quantitative estimation of low-abundance lipids on membrane properties.

二酰基甘油（DAG）是一种生物活性脂质，普遍存在于细胞膜中，浓度低。在脂质重塑酶如磷脂酶C和磷脂酸磷酸酶活化后，DAG浓度增加，导致脂质膜的层状相破坏。为了研究这些现象的结构起源，这里我们为DAG开发了一个粗粒度模型，该模型能够正确地重现其物理化学特性，包括界面张力和触发速率。我们发现，即使在低浓度下，DAG分子的百分率也无法忽略，占据了叶间空间。在高浓度下，DAG分子会从层状脂质经历相分离过程，分离在仅DAG的水泡中，并有效减少外围酶可用的DAG表面池。我们的结果可以更好地理解DAG在细胞膜中的作用，并为定量评估低丰度脂质对膜特性的研究提供了新的工具。