Mechanical Control of Nuclear Genetic Messages

Organism health relies on key cellular events like division, migration, and differentiation. These universal processes depend on cytoplasmic reorganization, notably driven by the cytoskeleton and its force-generating motors. Their activity generates active force fluctuations that stir the cytoplasm, agitating and displacing membrane-bound organelles like mitochondria and the nucleus across cell types in various organisms. Changes in these intracellular forces were proposed to be key in embryogenesis and were also linked with the malignancy of cancer cells.

Although evidence in the literature indicates that cytoplasmic forces are transmitted inside the nucleus, it is generally assumed that they do not impact nuclear function. In this seminar, I will discuss our laboratory’s recent work, based on interdisciplinary and multiscale methodologies, that challenges this paradigm. Our research shows that these forces, by mechanically agitating the nucleus, remodel nuclear biomolecular condensates and regulate their RNA processing function in different cell types and contexts, as well as in vitro. Our findings support an original mechanism that functionally relates cytoplasmic forces to nuclear condensate dynamics, which, from a biophysical perspective, reflects the transduction of cytoskeletal forces across different cellular domains and scales. We propose that this mechanism may be implicated in condensate-related diseases, several of which intriguingly associate with altered cytoskeletal dynamics.