Modelos de membrana celular para aplicaciones biomédicas.

Adwan Al Chihabi, Lara
Cea Mingueza, Pilar (dir.) ; Martín Solans, Santiago (dir.)

Universidad de Zaragoza, CIEN, 2024

Máster en Materiales Nanoestructurados para Aplicaciones Nanotecnológicas (Nanostructured Materials for Nanotechnology Applications)

Abstract: Analysing the interactions of xenobiotics, pharmaceutical agents, nanoparticles, or other agents with cell membranes is a challenging process, largely due to the structural and functional complexity of cell membranes. To overcome these challenges, fundamental research often employs artificially assembled model cell membranes, which allow precise control over their composition and properties. In this Final Master’s thesis, the Langmuir technique is used to model the plasma membrane of healthy and inflammatory bowel disease-affected colonocytes at the air-water interface. These model membranes are used to investigate their interactions with [6]-Gingerol, a xenobiotic well-known for its antioxidant, anti-inflammatory, and antitumoral properties as well as its protective role in patients with inflammatory bowel disease (IBD). However, the low water solubility of [6]-Gingerol severely restricts its bioavailability, and thus its use as a therapeutic agent. This Final Master’s objective is to gather information about the molecular interactions between [6]-Gingerol and the components of plasma membranes, which could lay the groundwork for future development of delivery systems (e.g. liposomes or artificial exosomes) aimed at enhancing the therapeutic potential of [6]-Gingerol. In addition, the analysis of the interactions of [6]-Gingerol with healthy and disturbed model cell membranes could also contribute to a better understanding of the therapeutic effect of this xenobiotic. The influence of [6]-Gingerol in membrane fluidity, stability, and thermodynamic properties was assessed through the data retrieved from surface pressure-area per molecule isotherms. Results indicate that higher χGIN values increase membrane fluidity. From a thermodynamic point of view, both systems exhibit repulsive interactions between [6]-Gingerol and membrane components, which are generally stronger in the healthy membrane (HM). Incorporation of [6]-Gingerol into both model membranes was also studied using adsorption experiments in which surface pressure measurements were analysed, and by means of the in situ visualization of the monolayers at the air-water interface using Brewster Angle Microscopy (BAM). In conclusion, [6]-Gingerol is capable of penetrating both model membranes, exhibiting a more favourable incorporation in the HM membrane as opposed to the IBD-affected one. All these findings highlight the distinct thermodynamic and structural behaviour of [6]-Gingerol interactions with healthy versus IBD-affected membrane models, contributing to a deeper understanding of the impact of [6]-Gingerol on plasma membrane properties.

Tipo de Trabajo Académico: Trabajo Fin de Master