Investigation of a reciprocal feedback between the transport and the cellular mechanostat functions of the nuclear envelope

• Applicant: Professor Dr. Wolfgang Linke, since 11/2022
• Subject Area: Biochemistry ; Anatomy and Physiology ; Cell Biology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 406295714

The role of the nuclear envelope as a selective barrier between the cytoplasm and the nucleus has been well established. In the last two decades another critical function of the nuclear envelope has become increasingly appreciated. Multiple mutations of the structural components of the nuclear envelope associated with debilitating clinical manifestations have illustrated the pivotal role of the nuclear envelope for sensing and processing mechanical inputs from the environment. Nevertheless, a possibility of a functional reciprocal feedback between the barrier and the cellular mechanostat functions of the nuclear envelope remains virtually unexplored. During the course of our preliminary work a technological platform has been established enabling us to monitor and actively modulate both the barrier function and the mechanical state of the nucleus of endothelial cells. The data acquired so far indicates that the unbalanced gradients of pressure across the nuclear envelope are indeed able to drive material transport across the nuclear envelope. Critically, the buildup of the pressure gradient depends on the integrity of the nucleocytoplasmic barrier. This in turn implies that the barrier function of the nuclear envelope may influence the overall mechanics of the nucleus playing a role of a fast-response cellular mechanostat. Therefore, the aim of this project is to further investigate a putative reciprocal feedback mechanism between the barrier and the cellular mechanostat functions of the nuclear envelope. The data resulting from the proposed experimental program may help us generate a novel view of the physiology of a eukaryotic cell nucleus and expand our knowledge on the interplay between the mechanical forces and the barrier function of the nuclear envelope.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Ivan Liashkovich, until 11/2022