• Résumé en Français:

Tissue cells are affected by mechanical forces at different lengths and timescales, and these intracellular and extracellular mechanical signals affect the evolution of cell life. However, although the mechanics of the cell as a whole is now a fairly well-studied subject, we still lack a detailed understanding of the mechanisms by which these mechanical stresses are transmitted to the nucleus of the cell, and what the effects of mechanical deformation are on nuclear processes, involving the (re)organisation of chromatin and possibly downstream genetic functions associated with DNA.The DNASTRIX project aims to study and quantify how nuclear mechanics can be modified by forces from the cellular environment, and what are the key genomic implications of these mechanical processes, from the cellular to the molecular scale, potentially involved in many human diseases. To achieve such ambitious goals, we will push the boundaries of a set of innovative techniques based on micro-electro-mechanical systems (MEMS) devices, under active development in our laboratories, by which we can apply controlled forces to both molecular aggregates, and whole living cells, while performing real-time fluorescence and confocal imaging. In parallel, we will exploit a theoretical and computational molecular dynamics modelling programme (atomic and coarse-grained) of the key proteins involved in the mechanical actions transmitted to chromatin, as well as micromechanical modelling of whole cells, to elucidate the multi-scale details of the transfer of mechanical stresses to nuclear constituents. The objectives of this project are therefore twofold and parallel: (1) to observe and quantify the link between extranuclear cellular structures and the nucleus; (2) to reorganise chromatin and identify possible damage to chromatin and DNA induced by mechanical forces.

• Résumé en Anglais:

Tissue cells are affected by mechanical forces at different lengths and timescales, and these intracellular and extracellular mechanical signals affect the evolution of cell life. However, although the mechanics of the cell as a whole is now a fairly well-studied subject, we still lack a detailed understanding of the mechanisms by which these mechanical stresses are transmitted to the nucleus of the cell, and what the effects of mechanical deformation are on nuclear processes, involving the (re)organisation of chromatin and possibly downstream genetic functions associated with DNA. The DNASTRIX project aims to study and quantify how nuclear mechanics can be modified by forces from the cellular environment, and what are the key genomic implications of these mechanical processes, from the cellular to the molecular scale, potentially involved in many human diseases. To achieve such ambitious goals, we will push the boundaries of a set of innovative techniques based on micro-electro-mechanical systems (MEMS) devices, under active development in our laboratories, by which we can apply controlled forces to both molecular aggregates, and whole living cells, while performing real-time fluorescence and confocal imaging. In parallel, we will exploit a theoretical and computational molecular dynamics modelling programme (atomic and coarse-grained) of the key proteins involved in the mechanical actions transmitted to chromatin, as well as micromechanical modelling of whole cells, to elucidate the multi-scale details of the transfer of mechanical stresses to nuclear constituents. The objectives of this project are therefore twofold and parallel: (1) to observe and quantify the link between extranuclear cellular structures and the nucleus; (2) to reorganise chromatin and identify possible damage to chromatin and DNA induced by mechanical forces.