We aim at developing pure and hybrid protein-based materials for the delivery of small molecules and therapeutics. We go from the detailed design and the characterization of the materials to the final application in in vitro and in vivo models. We perform studies of the structure (X-ray techniques and Infrared spectroscopy), dynamics (Neutron Scattering) and physico-chemical properties (microscopy) of the materials and we combine them with cell studies for the evaluation of the delivery capability and potential cytotoxicity.
On this topic, we closely collaborate with Hanne Mørck Nielsen, Mingshi Yang and Marco van de Weert (University of Copenhagen, DK), Ioannis S. Chronakis (DTU Food, DK), Stefano Pagliara (University of Exeter, UK). We also support with our expertise in X-ray scattering Lorenzo Di Michele (University of Cambridge, UK) for the developing of programmable DNA-based materials.
Brady R. et al 2018 JACS 140, 15384–15392 [LINK]
Vetri V. et al. 2018 J Phys Chem B 122, 3101-3112 [LINK]
Biomaterials for Drug Delivery (2017- Today)
The interaction between biomolecules and biological membranes rules the function of biological systems. We focus on both natural and model membranes and we are particularly interested in the biophysics of the membrane upon interactions with proteins and nanoparticles. In collaboration with Valeria Vetri (University of Palermo), we develop advanced microscopy approaches to study the formation of hybrid lipid-protein structures. With Bente Vestergaard (University of Copenhagen) and in the context of neurodegenerative diseases, we focus on how the physical properties of the membranes affect the binding of disease-related proteins as alpha-synuclein, with an emphasis on the effect of curvatures and membrane composition. With Lorenzo di Michele (University of Cambridge), we use flickering spectroscopy to evaluate the microscopic modification of the membranes in the presence of different aggregate states, both for model and pathological proteins.
Borro B.C. et al. 2017 Phys. Chem. Chem. Phys. 19, 27930 [LINK]
Di Carlo MG et al. 2016 Biophys Chem, 216, 23-30 [LINK]
Nors Pedersen M. et al. 2015 Scientific Reports, 5, 10422 [LINK]
van Maarschalkerweerd A et al. 2014 Biomacromol. 15, 3643 [LINK]
Biophysics of Protein-Membrane Interaction (2014- Today)
Protein and Peptide Self-Assembly (2006- Today)
The formation of protein aggregates is determined by a complex interconnection of steps appearing at different time and length scales. We study the kinetics of formation of aggregates for model proteins with the aim of disentangling the different concurrent events during the reaction. We use a combination of UV-Vis spectroscopy, super-resolution microscopy, statistical mechanics models, computer simulations and microfluidics-setup to quantitative detect the early unfolding events and connect them to the supramolecular aggregation, the structure and, most importantly, to the polymorphism of the aggregates.
We have several collaborators on this research branch: Nikos Hatzakis (University of Copenhagen, DK), Valeria Vetri (University of Palermo), Martin Weik (IBS, Grenoble, FR) Alessio Zaccone (University of Milan, IT).
Vetri V. et al. 2015 FEBS Lett, 589, 2448 [LINK]
Foderà V. et al. 2014 J Phys Chem Lett, 5, 3254 [LINK]
Di Michele L. et al. 2013 J Phys Chem Lett, 4, 3158 [LINK]
Foderà V., et al. 2013 Phys Rev Lett, 111, 108105 [LINK]
Foderà V. et al. 2012 J Phys Chem Lett, 3, 2803 [LINK]
Protein Particles in Drug Formulations (2018- Today)
Protein particles may be associated with an increased risk of immunogenic events, this being a serious concern in protein therapeutic injectables. The risk assessment during the protein drug product development is a challenge mainly because very little is known on the relationship between the protein particle structure and morphology and its potential immunogenicity. In collaboration with Novo Nordisk A/S, we aim at developing robust protocols for the analysis of homogeneous protein particle populations and connect specific characteristics to their immunogenicity.