Study of $p$H-dependent structural properties of transfection lipids layers for RNA delivery.

Grava M., Mohd I., Pusterla J., Schwierz N., Schneck E.
  Giovedì 15/09   09:00 - 13:00   Aula E - Rosalind Franklin   V - Biofisica e fisica medica   Presentazione
The most effective messenger RNA (mRNA) delivery systems are cationic lipid-based nanoparticles. This technology holds much promise for a broader use in biomedical applications, especially for patient-specific cancer treatments and vaccines. However, the transfection efficiency depends on the physicochemical properties of the lipid molecules, specifically on their charge and its dependence on $p$H. In order to determine their $p$H-dependent structural properties, $p$H-induced changes in internal molecular organization, and the protonation degree of monolayers of positively chargeable transfection lipid mixtures, we combine synchrotron-based X-ray scattering and X-ray fluorescence with atomistic molecular-dynamics simulations. The experimental techniques allow to discover the peculiarities on the lipids-RNA interactions by studying lipid surface charge and electron density profiles, while complementary molecular-dynamics simulations help to investigate the conformations of the lipid species, the area per molecule and the distribution of counterions.