Biology subjects

Bonnemay, L.

Publications and source records attributed to Bonnemay, L..

3 recordsLinked to original sources

bioRxiv2026

Uncoupling microtubule lifetime, stability and post-translational modifications.

Microtubules (MTs) undergo continuous cycles of growth and disassembly. Because the transitions between these states are stochastic, MT age varies widely within a population. As MTs age, they are thought to accumulate post-translational modifications (PTMs) that, directly or indirectly, enhance their stability and thereby extend their lifetime. The rare MTs that withstand prolonged exposure to destabilizing drugs such as nocodazole (NZ) are indeed enriched in PTMs; yet the relationships between MT age, PTMs and stability remain unclear. Using microinjection of labelled tubulin, we measured microtubule network turnover in immortalized mouse embryonic fibroblasts. Half of the network was renewed within 3 minutes and 80% within 10 minutes, while approximately 5% of microtubules persisted for more than 20 minutes. These dynamics were comparable in quiescent and senescent cells, although the fraction of slowly renewing or non-renewing microtubules rose to 20% in senescent cells. Unexpectedly, neither the amount of PTMs (acetylation and detyrosination) nor resistance to NZ increased with MT age, and resistance to NZ was independent of these PTMs. Degrees of acetylation and detyrosination should therefore not be taken as readouts of MT age or stability. Because these PTMs do not accumulate on MTs over time, the chemical modification of polymerized tubulin is likely more reversible and dynamic than previously assumed.

cell biology↗

bioRxiv2025

Filament transport supports contractile steady states of actin networks.

In all eukaryotic cells, the actin cytoskeleton is maintained in a dynamic steady-state. Actin filaments are continuously displaced from cell periphery, where they assemble, towards the cells center, where they disassemble. Despite this constant flow and turnover, cellular networks maintain their overall architecture constant. How such a flow of material can support dynamic yet steady cellular architectures remains an open question. To investigate the role of myosin-based forces in contractile steady-states of actin networks, we used a reconstituted in vitro system based on a minimal set of purified proteins, namely actin, myosin and actin regulators. We found that, contrary to previous bulk experiments, when confined in microwells, the actin network could self-organize into ordered arrangements of contractile bundles, flowing continuously without collapsing. This was supported by three-dimensional fluxes of actin filaments, spatially separated yet balancing each other. Unexpectedly, maintaining these fluxes did not depend on filament nucleation or elongation, but solely on filament transport. Ablation of the contractile bundles abolished the flux balance and led to network collapse. These findings demonstrate that the dynamic steady state of actin networks can be sustained by filament displacement and recirculation, independently of filament assembly and disassembly. Significance StatementCellular structures continuously self-renew, with new material constantly being added and removed while maintaining overall structural stability. This is particularly true for the actin cytoskeleton, whose components are continuously assembled, displaced, and reassembled. Understanding this process is fundamental to uncovering how cells regulate their architecture and adapt to stimuli. Here, we reconstitute an in vitro actomyosin network capable of contracting steadily over time without collapsing, relying solely on myosin-based transport. These findings demonstrate that a minimal system consisting of actin and molecular motors can effectively recapitulate the ability of actin networks to self-organize into stable yet dynamic architectures.

biophysics↗

bioRxiv2024

AML patient blasts exhibit polarization defect upon interaction with bone marrow stromal cells.

Hematopoietic stem and progenitor cells (HSPCs) establish specific interactions with bone marrow stromal cells, leading to their polarization. Given the role of cell polarity in protection against tumorigenesis and the importance of the niche in hematological disorders such as acute myeloid leukemias (AMLs), we investigated the polarization capacities of leukemic blasts from patients. Using engineered micro-niches and centrosome position with respect to the contact site with stromal cells as a proxy for cell polarization, we showed that AML cell lines and primary cells from AML patient blasts were unable to polarize in contact with healthy stromal cells. In return, exposure to AML patient-derived stromal cells compromised the polarization of healthy adult HSPCs and AML blasts from patients. Using live cell imaging in engineered "bone-marrow-on-a-chip", we further revealed that stromal cells from a leukemic niche increased the migration speed and distance of healthy HSPCs and AML blast as compared to their behavior in contact with healthy stromal cells. The results collectively demonstrated the respective influences of intrinsic AML blast transformation and extrinsic contact with AML stromal cells on the defective polarization of AML blast. They suggested that leukemic progression is associated with cell polarization defects and proposed new methodological approaches to investigate this relationship in AML progression.

cancer biology↗