We are active in the field of molecular simulations of cell penetrating peptides internalisation mechanisms. Cell-penetrating peptides (CPPs), such as TAT, polyarginine or penetratin, are short, positively charged amino acid sequences, that allow direct translocation of bioactive cargoes across cellular membranes. This property has been used in fundamental and applied biology since the end of the 1980’s to deliver a variety of compounds into cells. Recent studies have investigated the CPP potential to treat human diseases, such as wound healing, heart attack, and inflammation. However, our incomplete understanding of the way CPPs enter cells hamper further development and improvement of CPP-derived compounds.
Figure : TAT-RasGAP interacting with inner-like membrane. In red is shown the PS lipids and in blue the PIP2 lipids.
– E. Trofimenko, G. Grasso, M. Heulot, N. Chevalier, M. A Deriu, G. Dubuis, Y. Arribat, M. Serulla Llorens, S. Michel, G. Vantomme, F. Ory, J. Puyal, F. Amati, A. Lüthi, A. Danani, and C. Widmann, “Genetic, cellular and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore”, submitted to Nature Chemical Biology
– M. Serulla, G. Ichim, F. Stojceski, G. Grasso, S. Afonin, T. Schober, R. Roth, C. Godefroy, P.E. Milhiet, K. Das, A.G. Saez, A. Danani and C. Widmann, “TAT-RasGAP 317-326 kills cells by targeting inner leaflet-enriched phospholipids”, PNAS , DOI: 10.1073/pnas.201410811
– G. Grasso, S. Mercuri, A. Danani , M. A. Deriu, “Biofunctionalization of Silica Nanoparticles with Cell Penetrating Peptides: Adsorption Mechanism and Binding Energy Estimation”, J. Phys. Chem. B(2019) 123(50):10622-10630. DOI: 10.1021/acs.jpcb.9b08106.
– G. Grasso, S. Muscat, M. Rebella, A. Audenino, U. Morbiducci, A. Danani, M.A. Deriu, “Cell Penetrating Peptide Modulation of Membrane Biomechanics by Molecular Dynamics”, Journal of Biomechanics, May 2018, DOI: 10.1016/j.jbiomech.2018.03.036
– G. Grasso, M. A. Deriu, M. Prat, L. Rimondini, E. Vernè, A. Follenzi, and A. Danani, “Cell Penetratin Peptide Adsorption on Magnetite and Silica Surfaces: a computational investigation”, J. Phys. Chem. B, 2015, 119 (26), 8239–8246