Illuminating the complexity with X-rays, neutrons and light: structural insights into self-assembled lipid systems, from microemulsions to lipid-DNA nanoassemblies

Abstract:

Advanced materials designed for technological and healthcare applications often have complex structures that challenge their understanding. Small-Angle X-ray and Neutron Scattering (SAXS and SANS) address these challenges by offering crucial insights into nano-scale structures and morphologies. Specifically, SANS allows for selective visibility through deuteration techniques, effectively highlighting specific material components while rendering others invisible. In contrast, Fluorescence Cross-Correlation Spectroscopy (FCCS) utilizes visible light to quantify interactions between strategically selected labeled components, revealing colocalization and interactions within complex systems. Together, these methods provide a robust multimodal approach for probing and advancing our understanding of advanced materials.

In the first part of this talk, we will present two case studies: the first examines the structure of oil-in-water microemulsion droplets through partial deuteration, elucidating both droplet size and surfactant layer thickness. The second investigates the arrangement of DNA within contrast-matched multi-layered cationic liposomes (lipoplexes).

We will then explore how FCCS, by tagging DNA and liposomes with two distinct fluorophores, can simultaneously measure DNA encapsulation efficiency and the average number of DNA molecules per nanoparticle.

Finally, we will demonstrate how microfluidic devices, combined with in-situ SAXS, can assess the dissolution behaviors of lamellar liquid crystals under flow. Depending on the solvent, we observe either a surface erosion process, where the outer layers dissolve while the core remains intact, or a mixed surface-bulk erosion process, where both the core and surface dissolve. This methodology could be extended to elucidate the degradation behaviors of nanomedicines within small blood vessels.

Biography: 

Bruno Silva earned his PhD in Chemistry from the University of Porto, with an emphasis on colloidal physical chemistry. In 2010, he won a Marie Curie fellowship for postdoctoral research at the University of California Santa Barbara and Lund University, focusing on the structures of cationic liposome-DNA nanoparticles and on microfluidic devices with in-situ Small-Angle X-ray Scattering (SAXS) for studies of soft matter under flow and out-of-equilibrium conditions.

From 2015 to 2022, he led a research team at the International Iberian Nanotechnology Laboratory (INL), and in January 2023 he joined Empa, the Swiss Federal Laboratories for Materials Science and Technology, as a junior group leader. There he aims to advance the understanding of new generation nonviral gene delivery systems, focusing on structural and colloidal properties through innovative analytical methodologies based on SAXS and Fluorescence Cross-Correlation Spectroscopy (FCCS). To learn more, visit: https://www.empa.ch/web/s499/b.-silva-personal-page