Biology subjects

Dolega, M. E.

Publications and source records attributed to Dolega, M. E..

4 recordsLinked to original sources

bioRxiv2026

The nucleolus is a mechanosensitive condensate that adapts ribosome biogenesis to mechanical forces

Intracellular compartmentalization is fundamental to cellular organization, yet mechanobiology has been largely understood through membrane-delimited structures and associated signaling pathways. Whether mechanical forces directly regulate biomolecular condensates, which organize many core cellular functions, remains largely unknown. This question is particularly relevant for the nucleolus, a prominent nuclear condensate that coordinates ribosome biogenesis and is known to remodel in response to diverse biochemical perturbations, placing it at the interface between cellular state and biosynthetic control. Here, we show that mechanical compression remodels nucleolar organization and reduces (ribosomal DNA) rDNA transcription, and identify nucleolin as a key mediator of this adaptive response. Compression induces rapid and reversible redistribution of nucleolin from the nucleolus to the nucleoplasm, accompanied by reduced occupancy at rDNA promoter regions and changes in rDNA transcription and precursor rRNA processing. The nucleolar response occurs independently of classical post-translational regulation of nucleolin and instead depends on the rate of nuclear deformation, with nucleolar organization and function scaling with nuclear volume loss, supporting a mechanism of biophysical regulation. Together, our findings establish the nucleolus as a mechanosensitive condensate and reveal dual regulation of ribosome biogenesis by mechanical compression, through rapid nucleolin-based biophysical adaptation followed by slower epigenetic remodeling.

cell biology↗

bioRxiv2025

Mechanosensitive and Reversible Chromatin-Lamina Dewetting Triggers Cellular Contraction During Wound Healing

Tissue wounding causes rapid mechanical changes in the epithelium, but how these changes affect intracellular organization remains unclear. Using the Drosophila embryonic epidermis, we show that wounding induces a fast, transient compaction of chromatin and its detachment ("dewetting") from the nuclear lamina in about half of the wound-edge cells. Within minutes, chromatin in these cells re-expands and re-associates with the lamina ("re-wetting"). This reversible chromatin-lamina dewetting is mechanosensitive, requiring both the LINC complex and intracellular calcium. During compaction, calcium is stored within chromatin and is later released during ATR-mediated expansion and lamina re-wetting. Chromatin re-expansion then triggers actomyosin contraction and promotes tissue repair through Jun kinase activation, straightening of the wound edge, and supracellular actin ring formation. Together, our findings reveal a multiscale mechanosensitive mechanism by which tissue-scale mechanical changes induce a reversible chromatin-lamina dewetting, leading to cellular contraction and initiation of tissue repair.

cell biology↗

bioRxiv2025

Mechanical Stress dissipation in locally folded epithelia is orchestrated by calcium waves and nuclear tension changes

Epithelia are continuously exposed to a range of biomechanical forces such as compression, stretch and shear stress arising from their dynamic microenvironments and associated to their function. Changes in tension such as stretch are known to trigger cell rearrangements and divisions, and impact cellular transcription until mechanical stress is dissipated. How cells process, adapt and respond to mechanical stress is being intensively investigated. In here we focus on epithelial folding which is the fundamental process of transformation of flatmonolayers into 3D functional tissues. By combining the innovative method for fold generation, live imaging, mechanobiology tools and chemical screening, we uncover the role of calcium waves on mechanical adaptation of folded epithelia that occurs at the tissue and nuclear level. Folding associated tensional load results in the nuclear flattening which is recovered in the time scale of minutes and is dependent on the calcium wave that spread outwards from the channel and across the epithelium. By creating a mutant overexpressing LBR that relaxed nuclear envelope, we demonstrated that despite presence of calcium waves, nuclear tension increase was essential to trigger nuclear shape recovery post folding through the activation of cellular contractility in the cPLA2 dependent manner. Overall our results identify the molecular mechanism for nuclear shape recovery and indicate that mechanical stress dissipation program is activated at the level of nuclei which serve as internal tension sensors.

developmental biology↗

bioRxiv2018

Extracellular Matrix acts as pressure detector in biological tissues

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions 1-5. To perceive mechanical perturbations of different types and magnitudes, tissues need a range of appropriate detectors 6-8, with a compliance that has to match the perturbation amplitude. As a proxy of biological tissues, we use multicellular aggregates, a composite material made of cells, extracellular matrix and permeating fluid. We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9-13, while the same amount of selective compression on cells has almost no effect 14,15. We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space. This description correctly predicts the emergent bulk modulus of the aggregate as well as the hydrodynamic diffusion coefficient of the percolating interstitial fluid under compression. We further show that, on a longer timescale, the extracellular matrix serves as a sensor that regulates cell proliferation and migration in a 3D environment through its permanent deformation and dehydration following the global compression.

biophysics↗