| Abstract [eng] |
The immune system's ability to induce apoptosis in cancerous cells via lipid rafts is a promising avenue for cancer treatment. However, cancer cells with decayed rafts are unable to receive apoptosis signals. Therefore, studying lipid rafts, with their significant potential in developing anticancer drugs, could lead to novel therapeutic strategies. In previous studies, visualisation and mapping viscosity of model lipid rafts using BODIPY-C₁₂ encountered some challenges. However, a significant breakthrough was achieved when Polita et al. experimentally investigated a modified next-generation BODIPY-PM sensor. However, the dye's positioning was unclear, and the resulting biexponential decays were unexplained. Therefore, this master's thesis aims to calculate the physical parameters of the lipid membrane with the BODIPY sensor by applying computational chemistry models, which would allow us to evaluate the performance of the embedded sensor. The following tasks were set: prepare a suitable molecular mechanics force field for the sensor and the lipid membrane, perform a molecular dynamics simulation at constant temperature and pressure, determine the orientation of the sensor in the lipid membrane and calculate the in‑plane diffusion coefficient. In this study, we conducted molecular dynamics simulations using adequately prepared gaff and Amber lipid force fields on the BODIPY-PM sensor, which was inserted into the lipid membrane. The simulations unveiled the existence of two states of tilted BODIPY-PM in the lipid membrane, shedding light on the sensor's biexponential decay. The different tilt angles of BODIPY-PM affect the sensor's behaviour, leading to a change in the potential energy surface. In the liquid-ordered phase, the diffusion coefficient of BODIPY-PM is lower than in the liquid-disordered phase, indicating a higher viscosity. This increase in viscosity is attributed to the more ordered structure of the membrane and the additional interaction of BODIPY with cholesterol molecules. |
