Leite Natália Bueno, Martins Danubia Batista, Alvares Dayane S, Cabrera Marcia Perez Dos Santos
Departamento de Química e Ciências Ambientais, Universidade Estadual Paulista (UNESP), Instituto de Biociências Letras e Ciências Exatas (IBILCE), Câmpus São José do Rio Preto, SP, Brazil.
Departamentode Física, Universidade Estadual Paulista (UNESP), Instituto de Biociências Letras e Ciências Exatas (IBILCE), Câmpus São José do Rio Preto, SP, Brazil.
Chem Phys Lipids. 2022 Jan;242:105160. doi: 10.1016/j.chemphyslip.2021.105160. Epub 2021 Nov 20.
Quercetin is a polyphenolic molecule with a broad spectrum of biological activities derived from its antioxidant property. Its mechanism of action has been explained by its binding and/or interference with enzymes, receptors, transporters and signal transduction systems. Since these important mechanisms generally occur in membrane environments, within and through lipid bilayers, investigating the biophysical properties related to the diversity of lipid compositions of cell membranes may be the key to understanding the role of cell membrane in these processes. In this work, we explored the interaction of quercetin with model membranes of different lipid compositions to access the importance of lipid phases and bilayer homogeneity to the action of quercetin and contribute to the understanding of quercetin multiple activities. Analysis of the influence of quercetin on the morphology and permeability of GUVs, the rigidity of LUVs and affinity to these vesicles showed that quercetin strongly partitions to the more homogeneous environments, but significantly permeates and modifies the more heterogeneous where liquid-disordered, liquid-ordered and solid phases coexist. Our findings support the condensing effect of quercetin, which is observed through a significant rigidifying of bilayers containing 40% cholesterol, but much less evidenced when it is reduced to 20% or in its absence. Nevertheless, the presence of sphingomyelin in the ternary system led to a more heterogeneous bilayer with the formation of micrometric and probably also nanometric domains, which coalesce in the presence of quercetin. This observation together with increased permeability points to an insertion effect.
槲皮素是一种具有广泛生物活性的多酚类分子，其生物活性源于其抗氧化特性。其作用机制已通过其与酶、受体、转运蛋白和信号转导系统的结合和/或干扰来解释。由于这些重要机制通常发生在膜环境中，即在脂质双层内部并通过脂质双层，研究与细胞膜脂质组成多样性相关的生物物理特性可能是理解细胞膜在这些过程中作用的关键。在这项工作中，我们探索了槲皮素与不同脂质组成的模型膜之间的相互作用，以了解脂质相和双层均匀性对槲皮素作用的重要性，并有助于理解槲皮素的多种活性。对槲皮素对巨型单层囊泡（GUVs）的形态和通透性、小单层囊泡（LUVs）的刚性以及对这些囊泡的亲和力的影响分析表明，槲皮素强烈地分配到更均匀的环境中，但能显著渗透并改变更不均匀的环境，即液相无序、液相有序和固相共存的环境。我们的研究结果支持了槲皮素的凝聚作用，这在含有40%胆固醇的双层膜显著硬化中观察到，但当胆固醇含量降至20%或不存在时，这种作用就不太明显了。然而，三元体系中鞘磷脂的存在导致形成了更不均匀的双层膜，并形成了微米级甚至可能还有纳米级的结构域，这些结构域在槲皮素存在时会合并。这一观察结果以及通透性的增加表明存在插入效应。
