Exploring the physicochemical properties of the integration of Tristearoyl uridine in Langmuir monolayers: An approach to cell membrane modeling for prodrugs

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Felipe Almeida Moreira , Jhon Fernando Berrío Escobar , Cristiano Giordani , Luciano Caseli
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Abstract

Understanding the mechanisms by which drugs interact with cell membranes is crucial for unraveling the underlying biochemical and biophysical processes that occur on the surface of these membranes. Our research focused on studying the interaction between an ester-type derivative of tristearoyl uridine and model cell membranes composed of lipid monolayers at the air-water interface. For that, we selected a specific lipid to simulate nontumorigenic cell membranes, namely 1,2-dihexadecanoyl-sn-glycero-3-phospho-l-serine. We noted significant changes in the surface pressure-area isotherms, with a noticeable shift towards larger areas, which was lower than expected for ideal mixtures, indicating monolayer condensation. Furthermore, the viscoelastic properties of the interfacial film demonstrated an increase in both the elastic and viscous parameters for the mixed film. We also observed structural alterations using vibrational spectroscopy, which revealed an increase in the all-trans to gauche conformers ratio. This confirmed the stiffening effect of the prodrug on the lipid monolayer. In summary, this study indicates that this lipophilic prodrug significantly impacts the lipid monolayer's thermodynamic, rheological, electrical, and molecular characteristics. This information is crucial for understanding how the drug interacts with specific sites on the cellular membrane. It also has implications for drug delivery, as the drug's passage into the cytosol may involve traversing the lipid bilayer.

Abstract Image

探索三苯甲酰基尿苷在朗缪尔单层中整合的物理化学特性:原药细胞膜建模方法
了解药物与细胞膜相互作用的机制对于揭示发生在这些膜表面的潜在生物化学和生物物理过程至关重要。我们的研究重点是研究三苯甲酰基尿苷的酯类衍生物与由脂质单层组成的模型细胞膜在空气-水界面上的相互作用。为此,我们选择了一种特定的脂质来模拟非致癌细胞膜,即 1,2-二十六碳酰-sn-甘油-3-磷-l-丝氨酸。我们注意到表面压力-面积等温线发生了重大变化,明显向更大面积转变,低于理想混合物的预期,表明存在单层凝结。此外,界面薄膜的粘弹特性表明,混合薄膜的弹性和粘性参数都有所增加。我们还利用振动光谱观察到了结构的变化,发现全反式与高顺式构象比有所增加。这证实了原药对脂质单层的增硬作用。总之,这项研究表明,这种亲脂原药对脂质单分子层的热力学、流变学、电学和分子特性有显著影响。这些信息对于了解药物如何与细胞膜上的特定位点相互作用至关重要。由于药物进入细胞膜可能需要穿越脂质双分子层,因此这对药物输送也有影响。
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来源期刊
Biophysical chemistry
Biophysical chemistry 生物-生化与分子生物学
CiteScore
6.10
自引率
10.50%
发文量
121
审稿时长
20 days
期刊介绍: Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.
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