Biology subjects

Ribba, A.-S.

Publications and source records attributed to Ribba, A.-S..

3 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↗

bioRxiv2026

Winding-Up of Fibrin Fibers as a Novel Mechanism of Platelet-Mediated Fiber Compaction

This study reveals a previously unrecognized mechanism by which platelets retract and compact fibrin fibers. Using a newly developed 2D fiber-retraction assay, we observed an initial "gearwheel" pattern of actin-myosin organization in spread platelets with associated, extracellular fibrin patches that appear to form an initiation complex for fibrin fiber attachment and rearrangement. The final outcome of this process results in two morphologically different platelet populations. Spread platelets with coiled fibers around and above their pseudo-nucleus. Other platelets are only partially spread on the glass surface and are surrounded by tightly packed fibrin fibers around bulbous protrusions ("bulbs"), mirroring the architecture of platelets and adjacent fibers within a retracted clot. Thus, the observed compaction process might also take place during clot retraction in order to reduce clot volume, stiffen the clot and enhance wound repair. Apart from pulling on fibers like on a rope, platelets actively wrap fibrin fibers into compact structures, similar to balls of wool. Besides DNA packaging, this represents a new example of a natural fiber compaction mechanism. Using a combination of 3D clot-retraction and 2D fiber-retraction assays, expansion and electron microscopy, live imaging and mathematical modeling, we show that platelets use an actomyosin-driven motion to gather and loop fibrin fibers around the base of bulbous protrusions. These bulbs form when a platelet becomes trapped between fibrin fibers during 3D clot retraction or 2D fiber-retraction assays. These findings complement and extend earlier models of platelet-mediated fibrin fiber retractions, offering new insight into how platelets mechanically organize fibrin fibers.

cell biology↗

bioRxiv2020

Two antagonistic microtubule targeting drugs act synergistically to kill cancer cells

Paclitaxel is a microtubule stabilizing agent and a successful drug for cancer chemotherapy inducing, however, adverse effects. To reduce the effective dose of paclitaxel, we searched for drugs which could potentiate its therapeutic effect. We have screened a chemical library and selected Carba1, a carbazolone, which exerts synergistic cytotoxic effects on tumor cells grown in vitro, when co-administrated with a low dose of paclitaxel. Carba1 targets the colchicine binding-site of tubulin and is a microtubule-destabilizing agent. The Carba1-induced modulation of microtubule dynamics increases the accumulation of fluorescent paclitaxel inside microtubules, providing a mechanistic explanation of the observed synergy between Carba1 and paclitaxel. The synergistic effect of Carba1 with paclitaxel on tumor cell viability was also observed in vivo in xenografted mice. Thus, a new mechanism favoring paclitaxel accumulation in microtubules can be transposed to in vivo mouse cancer treatments, paving the way for new therapeutic strategies combining low doses of microtubule targeting agents with opposite mechanisms of action.

cancer biology↗