Research

During my research career, I have been involved in quite different aspects of protein biophysics. My path has been relatively ecletic, but with a definite trait d'union: understanding proteins as dynamical chamaleontic systems which can populate lots of dramatically different structures.

Single molecule AFM force spectroscopy

Relationship between mechanical and redox switches in angiostatin

• Grandi F.#, Sandal M.# Guarguaglini G., Capriotti E., Casadio R., Samorì B. Hierarchical mechanochemical switches in Angiostatin, ChemBioChem 2006, 7,1774-1782 (#=shared first)

In my initial research work, planned and started as an undergraduate, I revealed the presence of mechanical unfolding intermediates in the protein angiostatin, and associated to its disulfide redox state regulation by thioredoxin. The study suggested a novel cell signalling pathway that emerges from the integration of disulfide redox switches and cell migration mechanical forces. The work unveiled how out of equilibrium structures induced by mechanical forces could be of functional interest also for proteins not directly involved in muscle mechanics.

Conformational ensembles of amyloidogenic] proteins at the single molecule level

• Sandal M.#, Valle F.#, Tessari I., Mammi S., Bergantino E., Musiani F., Brucale M., Bubacco L., Samorì B. Conformational Equilibria in Monomeric Alpha-Synuclein at the Single Molecule Level, PLoS Biology 2008 6(1):e6 (#=shared first)

• Brucale M. , Sandal M. , Di Maio S., Rampioni A., Tessari I., Bubacco L., Samorì B. , Pathogenic Mutations Shift the Equilibria of alpha-Synuclein Single Molecules towards Structured Conformers , ChemBioChem 2009 Jan 5;10(1):176-83.

• Sorce B., Sabella S., Sandal M., Samorì B., Santino A., Cingolani R., Rinaldi R., Pompa P.P. Single-Molecule Mechanical Unfolding of Amyloidogenic beta(2)-Microglobulin: The Force-Spectroscopy Approach. ChemPhysChem 2009 Jun 3

I moved towards the experimental determination of the conformational ensembles that proteins populate at equilibrium, focusing on proteins prone to aggregation. I reported the first measurements of an intrinsically unstructured protein conformational equilibria by means of single-molecule force spectroscopy. We reported that shifts in the population of one of the conformational basins are linked to the protein aggregation propensity. The approach that I developed has been recognized as a promising methodology to the study of unstructured proteins1. The initial results that we obtained have been further validated by the study of naturally occuring pathogenic variants of alpha-synuclein and to the native-like aggregation of beta-2-microglobulin.