Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, 30100 Murcia, Spain.
Departamento de Medicina Legal y Forense, Facultad de Medicina, Instituto de Investigación Biomédica (IMIB-Arrixaca), Universidad de Murcia, 30120 Murcia, Spain.
Molecules. 2022 May 3;27(9):2910. doi: 10.3390/molecules27092910.
3,4,5-Trimethoxybenzoate of catechin (TMBC) is a semisynthetic catechin which shows strong antiproliferative activity against malignant melanoma cells. The amphiphilic nature of the molecule suggests that the membrane could be a potential site of action, hence the study of its interaction with lipid bilayers is mandatory in order to gain information on the effect of the catechin on the membrane properties and dynamics. Anionic phospholipids, though being minor components of the membrane, possess singular physical and biochemical properties that make them physiologically essential. Utilizing phosphatidylserine biomimetic membranes, we study the interaction between the catechin and anionic bilayers, bringing together a variety of experimental techniques and molecular dynamics simulation. The experimental data suggest that the molecule is embedded into the phosphatidylserine bilayers, where it perturbs the thermotropic gel to liquid crystalline phase transition. In the gel phase, the catechin promotes the formation of interdigitation, and in the liquid crystalline phase, it decreases the bilayer thickness and increases the hydrogen bonding pattern of the interfacial region of the bilayer. The simulation data agree with the experimental ones and indicate that the molecule is located in the interior of the anionic bilayer as monomer and small clusters reaching the carbonyl region of the phospholipid, where it also disturbs the intermolecular hydrogen bonding between neighboring lipids. Our observations suggest that the catechin incorporates well into phosphatidylserine bilayers, where it produces structural changes that could affect the functioning of the membrane.
3,4,5-三甲氧基苯甲酸表儿茶素酯（TMBC）是一种半合成儿茶素，对恶性黑色素瘤细胞具有很强的抗增殖活性。该分子的两亲性质表明，细胞膜可能是一个潜在的作用部位，因此，研究其与脂质双层的相互作用对于了解儿茶素对膜性质和动力学的影响是必不可少的。阴离子磷脂虽然是膜的次要成分，但具有独特的物理和生化性质，使它们在生理上必不可少。利用磷脂酰丝氨酸仿生膜，我们研究了儿茶素与阴离子双层之间的相互作用，结合了多种实验技术和分子动力学模拟。实验数据表明，该分子嵌入磷脂酰丝氨酸双层中，在双层中扰乱了热致凝胶向液晶相的相变。在凝胶相中，儿茶素促进了交错的形成，而在液晶相中，它降低了双层的厚度并增加了双层界面区域的氢键模式。模拟数据与实验数据一致，表明该分子作为单体和小簇存在于阴离子双层的内部，到达磷脂的羰基区域，在那里它还扰乱了相邻脂质之间的分子间氢键。我们的观察表明，儿茶素很好地融入了磷脂酰丝氨酸双层，在双层中产生了可能影响膜功能的结构变化。
