INSIGHTS FROM THE INTERACTION BETWEEN NANOPARTICLES AND LIPID BILAYERS MIMICKING HEALTHY AND UNHEALTHY CELL MEMBRANES.

The plasma membrane is a dynamic structure composed of a lipid bilayer that exhibits compositional asymmetry between its inner and outer leaflets. This asymmetry is crucial for several physiological processes, including membrane trafficking, cell signaling, and recognition. Despite its recognized importance, the understanding of this asymmetry at molecular level remains poorly understood. In this work, we explore two important aspects of the bilayer asymmetry related to the fraction of cholesterol and the presence of negatively charged lipids in the membrane outer leaflet. We explore how nanoparticles (NP1–NP5) affect the bilayer structures of symmetric biomembranes, specifically analyzing the features of healthy and unhealthy cell membrane models. To mimic a healthy cell, we prepare the outer leaflet of the membrane using a lipid composition that induce the coexistence of liquid phases, namely liquid disordered (Ld) and liquid ordered (Lo) phases. Here, we vary the size of domains and investigate how these nanoparticles interact with the outer leaflet models. To model unhealthy cells, a considerable fraction of phosphatidylserine (PS) comprises the outer leaflet of our biomembranes. Notably, tumor cells often expose PS on the outer leaflet, altering membrane behavior and susceptibility to nanoparticle penetration. Thus, our mimetic system of tumor cells is prepared with PS in the outer leaflet. Here we prepare giant unilamellar vesicles (GUVs) using the electroformation procedure, and gel-assisted method, and use a fluorescence microscope to investigate structural and morphological changes in the model bilayer. In addition, we examine the leakage of fluorescent trapped dye inside the GUV due to the interaction with nanoparticles. Preliminary results indicate that lipid composition and phase state strongly influence nanoparticle partitioning, membrane disruption, and dye leakage. Our findings reinforce the biological relevance of specific interactions between nanoparticles and lipids, providing a foundation for designing more efficient target systems for biomedical applications.