Among technology-derived nanomaterials, engineered nanoparticles have been extensively studied to develop novel applications in biology and medicine, including cancer treatment, bioimaging, biosensing, tissue engineering, drug and gene delivery. The majority of these biomedical applications lead to the inevitable interaction between nanoparticles and the cell membrane, which is the first biological barrier that nanoparticles encounter once introduced into the organism. Understanding nanoparticle-membrane interaction mechanisms is therefore a priority in the field, both to investigate the effects of nanoparticle on cell structure and function and to explore their use as synthetic agents for biomedical applications. In this context, several studies have demonstrated that functionalized gold nanoparticles are promising tools due to their remarkable core stability, surface functionalization versatility and compatibility with biological systems. This thesis investigates the interactions between biomimetic membranes and gold NPs with a sub-6nm core, functionalized with an amphiphilic coating. Biomimetic membranes provide a controlled and simplified environment to capture molecular details of the interactions that could hardly be studied in real biological membranes, which are too complex. A biophysical approach was employed in this study, using fluorescence spectroscopy, optical microscopy, quartz crystal microbalance measurements, small angle X-ray scattering, dynamic light scattering and zeta potential analysis. The physicochemical parameters governing gold nanoparticles as synthetic fusogenic agents were investigated using fluorescence assays and quartz crystal microbalance measurements, revealing how the nanoparticles can serve as a potential tool for artificial membrane fusion. Furthermore, the effects of nanoparticles on membrane properties were studied in different biomimetic systems to provide detailed and more complete insights into nanoparticle-membrane interactions. Changes in membrane morphology and permeability were investigated using optical microscopy on cell-sized vesicles. NP-membrane interaction in the presence of osmotic stress was studied using small angle X-ray scattering on small vesicles. Finally, in line with the aim of increasing biomimicry, an optimized protocol for asymmetric membranes with lipid compositions mimicking key features of eukaryotic cell membranes was developed, providing a platform for future studies of NP effects under biologically relevant conditions. Overall, the findings of this work broaden our understanding of various aspects of nanoparticle-membrane interactions from a fundamental perspective, highlighting key factors that may be relevant for the potential applications of amphiphilic-coated gold nanoparticles.
Nanoparticle-membrane interactions: insights from biomimetic models
LEONARDINI, BEATRICE
2026-06-03
Abstract
Among technology-derived nanomaterials, engineered nanoparticles have been extensively studied to develop novel applications in biology and medicine, including cancer treatment, bioimaging, biosensing, tissue engineering, drug and gene delivery. The majority of these biomedical applications lead to the inevitable interaction between nanoparticles and the cell membrane, which is the first biological barrier that nanoparticles encounter once introduced into the organism. Understanding nanoparticle-membrane interaction mechanisms is therefore a priority in the field, both to investigate the effects of nanoparticle on cell structure and function and to explore their use as synthetic agents for biomedical applications. In this context, several studies have demonstrated that functionalized gold nanoparticles are promising tools due to their remarkable core stability, surface functionalization versatility and compatibility with biological systems. This thesis investigates the interactions between biomimetic membranes and gold NPs with a sub-6nm core, functionalized with an amphiphilic coating. Biomimetic membranes provide a controlled and simplified environment to capture molecular details of the interactions that could hardly be studied in real biological membranes, which are too complex. A biophysical approach was employed in this study, using fluorescence spectroscopy, optical microscopy, quartz crystal microbalance measurements, small angle X-ray scattering, dynamic light scattering and zeta potential analysis. The physicochemical parameters governing gold nanoparticles as synthetic fusogenic agents were investigated using fluorescence assays and quartz crystal microbalance measurements, revealing how the nanoparticles can serve as a potential tool for artificial membrane fusion. Furthermore, the effects of nanoparticles on membrane properties were studied in different biomimetic systems to provide detailed and more complete insights into nanoparticle-membrane interactions. Changes in membrane morphology and permeability were investigated using optical microscopy on cell-sized vesicles. NP-membrane interaction in the presence of osmotic stress was studied using small angle X-ray scattering on small vesicles. Finally, in line with the aim of increasing biomimicry, an optimized protocol for asymmetric membranes with lipid compositions mimicking key features of eukaryotic cell membranes was developed, providing a platform for future studies of NP effects under biologically relevant conditions. Overall, the findings of this work broaden our understanding of various aspects of nanoparticle-membrane interactions from a fundamental perspective, highlighting key factors that may be relevant for the potential applications of amphiphilic-coated gold nanoparticles.
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