Défense de thèse de doctorat en sciences chimiques "peptide-nanomaterial"

Modified nanomaterials, such as graphitic (fullerene, carbon nanotubes (CNTs) and graphene) and inorganic surfaces, have recently emerged as new multifunctional platforms for application in nanomedicine and biology. In this thesis, going through three main examples I illustrate the computational techniques applied to comprehend and master protein/nanomaterial interfaces of new bio-hybrids designed to investigate and control the targeting and migration of cancer cells. Particularly, for the first time, with extensive classical and QM calculations, it is herein reported the investigation of the structural and dynamical properties of a non- covalent bioconjugate in which the monoclonal Cetuximab antibody (Ctx) is adsorbed on a CNT surface resulting in a cancer cells targeting agents. The experimental data are here complemented by atomistic detailed insights showing the formation of strong conjugates stabilized by hydrophobic interactions. Interestingly, the predicted structural models of CNT/Ctx conjugate were ultimately generalized thanks to the remarkable structural similarity of Ctx with antibodies of different isotypes.

Aiming at exploring graphene potentialities, I investigate further the devised functionalization of graphitic nanomaterial presenting the theoretical engineering of a Janus-type β-sheet, designed to attain the controlled non-covalent functionalization of graphene towards targeting applications. By simulating several β-sheet candidates adsorbed onto graphene, different interacting profiles were observed and the best candidate was selected. In a reverse approach, the theoretical design is now guiding the production of the β-sheet protein, that is now under experimental validation.

Finally, I extended the biohybrid construction approach to investigate the cellular migration of cancer cells on patterned gold . A biomimetic model surface made of self-assembled motogenic peptide immobilized on gold (Au) surfaces was designed and tested experimentally in our group. Classical MD simulations presented in this thesis importantly elucidate and rationalize the different organization and biological responses of the motogenic surfaces.