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Nuclear alteration in progeria are due to mechanics

In a paper just published in the Biophysical Journal, researchers from the Center for Complexity & Biosystems clarified why the morphology of the cell nucleus is altered in progeria patients, who suffer from accelerated ageing due to a mutation in the lamin A gene, yielding an altered form of the protein, named progerin. The study was coordinated by Caterina La Porta, Professor of General Pathology and group leader of the Oncolab group at the Department of Environmental Science and Policy of the University of Milan and by Stefano Zapperi professor of Theoretical Physics of Matter at the Department of Physics “Aldo Pontremoli”. The first authors are Maria Chiara Lionetti who carried out this study during her PhD thesis, performing all the experiments on a newly developed cellular model of progeria, and Silvia Bonfanti, a postdoctoral fellow who carried out numerical simulations of nuclear mechanics.

“Our study combining quantitative cell biology and simulations of computational models provides a clear understanding of the mechanisms underlying morphological nuclear alteration in progeria. In particular, we showed that the presence of a small amount of progerin is able to change the mechanical interactions between the nuclear shell and cytoskeletal/chromatin tethers, affecting the mechanical properties of the nucleus and chromatin organization,” said Stefano Zapperi. “We decided to study this pathology,” explains Caterina La Porta, “because we were intrigued by the fact that progerin is also expressed in cancer, the core research field of my group. We understood that in order to clarify the role of progerin in tumors, we should first explain its behaviour in progeria. There is a paradox here, since progeria is associated with accelerated aging, while tumor cells are in principle never aging ”. She then concludes “Now that we have a clearer picture of progeria, we are starting to understand the role of progerin in tumor cells”. These results will be described in a forthcoming paper.

The paper is published in the Biophysical Journal

Link to the paper:

www.sciencedirect.com

published on 2/2/2021