The deposition of fibrillar protein aggregates in human organs is the hallmark of several pathological states, including highly debilitating neurodegenerative disorders and systemic amyloidoses. In this work, we propose a new approach, based on the use of single-cell force spectroscopy applied to multifunctional substrates, to study the interaction between protein oligomers, cell membranes, and/or the extracellular matrix. We were able to quantify the affinity between both oligomer type and the cell membrane by measuring the mechanical work needed to detach the cells from the aggregates, and we could discriminate the contributions of the membrane lipid and protein fractions to such affinity. The fundamental role of the ganglioside GM1 in the membrane-oligomers interaction was also highlighted. Finally, we observed that the binding of toxic oligomers to the cell membrane significantly affects the functionality of adhesion molecules such as Arg-Gly-Asp binding integrins, and that this effect requires the presence of the negatively charged sialic acid moiety of GM1.

Toxic HypF-N oligomers selectively bind the plasma membrane to impair cell adhesion capability / Reinier Oropesa-Nunez, Sandeep Keshavan, Silvia Dante, Alberto Diaspro, Benedetta Mannini, Claudia Capitini, Cristina Cecchi, Massimo Stefani, Fabrizio Chiti, Claudio Canale. - In: BIOPHYSICAL JOURNAL. - ISSN 0006-3495. - STAMPA. - 114:(2018), pp. 1357-1367. [10.1016/j.bpj.2018.02.003]

Toxic HypF-N oligomers selectively bind the plasma membrane to impair cell adhesion capability

Benedetta Mannini;Claudia Capitini;Cristina Cecchi;Massimo Stefani;Fabrizio Chiti;
2018

Abstract

The deposition of fibrillar protein aggregates in human organs is the hallmark of several pathological states, including highly debilitating neurodegenerative disorders and systemic amyloidoses. In this work, we propose a new approach, based on the use of single-cell force spectroscopy applied to multifunctional substrates, to study the interaction between protein oligomers, cell membranes, and/or the extracellular matrix. We were able to quantify the affinity between both oligomer type and the cell membrane by measuring the mechanical work needed to detach the cells from the aggregates, and we could discriminate the contributions of the membrane lipid and protein fractions to such affinity. The fundamental role of the ganglioside GM1 in the membrane-oligomers interaction was also highlighted. Finally, we observed that the binding of toxic oligomers to the cell membrane significantly affects the functionality of adhesion molecules such as Arg-Gly-Asp binding integrins, and that this effect requires the presence of the negatively charged sialic acid moiety of GM1.
2018
114
1357
1367
Reinier Oropesa-Nunez, Sandeep Keshavan, Silvia Dante, Alberto Diaspro, Benedetta Mannini, Claudia Capitini, Cristina Cecchi, Massimo Stefani, Fabrizio Chiti, Claudio Canale
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1113777
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