Inducing nuclear deformation to study the effect of Lamin A-deficiency on DNA damage in the nucleus of living cells

Abstract

Microstructured devices have been recently recognized as a powerful tool in cell biology. In this work, we have exploited this technology to create different microstructures to mechanically confine cells with the overarching aim of understanding the interplay between Lamin A-deficiency and nuclear deformation. Lamin A is one of the main components of the nuclear lamina, a filamentous network that mechanically scaffolds the inner side of the nucleus. Importantly, Lamin A is mutated in Hutchinson'Gilford Progeria Syndrome (HGPS), a rare genetic disease that causes accelerated aging. In this thesis, we present our experimental approaches in which we have exposed human foreskin fibroblast (HFF-1) cells to mechanical confinement to observe and analyze the deformation of cell nuclei. Our results provide a promising step forward towards the study of the impact of nuclear deformation on lamin A.