Mechanobiology of the mammalian nuclear envelope

Adaptation of the cell nucleus to mechanical stress

The nucleus is the largest and stiffest organelle in the cell, yet it remains a highly plastic and dynamic structure. A key property of the nucleus is its ability to rapidly respond to various stimuli, both chemical and mechanical, that originate outside the cell. This responsiveness enables cells to modulate gene expression rapidly and precisely, allowing adaptation of the proteome and cellular functions to specific physiological demands. It is common for the nucleus to undergo drastic changes in its mechanical properties in diseases such as cancer or aging.

Although multiple mechanisms and signaling pathways have been identified that connect the nucleus to the extracellular environment (García-García et al., Nature Communications, 2022; Echarri A., Biomolecules, 2022), many fundamental questions remain unanswered. 

Using integrative bioinformatic and quantitative proteomic approaches, we have identified several nuclear proteins that respond to mechanical stimuli. Notably, some of these proteins localize to the nuclear envelope and remain poorly characterized. This research line aims to functionally characterize these mechanosensitive proteins and elucidate their roles in cellular and nuclear adaptation to mechanical stress (see right panel). To achieve this, we employ a multidisciplinary strategy combining molecular biology, biochemistry, functional genetics, and various omics-based approaches (see left panel), with the ultimate goal of uncovering how the nucleus senses and responds to mechanical challenges.