Biology subjects

Herve, L.

Publications and source records attributed to Herve, L..

4 recordsLinked to original sources

bioRxiv2026

Space partitioning by self-organized epithelial networks

Branching epithelia build supracellular networks that must simultaneously ensure connectivity, mechanical integrity, and efficient space partitioning, yet a general framework for how such networks form beyond the endothelial lineage has been lacking. Here we show that epithelial cells from multiple branching organs spontaneously self-organize into extended reticulate networks in simplified environments, revealing a conserved network-forming capacity. Combining wide-field lensless holographic imaging, deep-learning segmentation (EpiNet), and graph-theoretic analysis, we resolve a reproducible assembly sequence - contact initiation, clustering, percolation, and post-percolation relaxation - and quantify its geometry across scales. Actomyosin contractility controls both the growth of connectivity and the relaxation dynamics that set network geometry, tuning the effective cost of forming connections and thereby selecting between tree-like and reticulate topologies. After percolation, epithelial networks behave as active tension networks that progressively refine space partitioning toward centroidal, near-optimal configurations while maintaining a characteristic mesh size through continuous edge nucleation. These findings establish epithelial network formation as a generic, physically regulated mode of tissue self-organization and provide a quantitative framework linking single-cell mechanics, network topology, and space-partitioning dynamics, with implications for branching morphogenesis, organoid models, and tissue engineering.

biophysics↗

bioRxiv2026

Dual-stage inhibition of Plasmodium falciparum by a Skeletocutis derived fungal metabolite targeting Pyruvate Kinase II

Plasmodium falciparum resistance to current first line treatments is threatening at-risk populations and underscores the urgent need for novel therapeutic targets and drugs. P. falciparum pyruvate kinases I and II are two essential enzymes with distinct roles and subcellular localizations within the parasite. PfPyrKI is cytosolic, while PfPyrKII is found in the apicoplast, a specific organelle of Apicomplexa, where it is required for the production of (d)NTPs essential for apicoplast maintenance. We identify skeletocutin E, a Basidiomycete-derived metabolite, as a specific inhibitor of PfPyrKII. Skeletocutin E inhibits in vitro the activity of PfPyrKII with an IC50 of 0.52 {+/-} 0.08 {micro}M through a mixed inhibition mechanism and does not affect the activities of three human pyruvate kinases. Structure-activity relationship analyses using synthetic skeletocutin E analogues allowed us to identify the molecular determinants of this inhibition. Furthermore, determination of the quaternary structure of PfPyrKII by mass photometry, showed that this enzyme exists as monomers, dimers, and tetramers in equal proportions, revealing its singularity compared to other pyruvate kinases. Interestingly, skeletocutin E does not alter the distribution of the complexes, indicating that it does not interact at the subunit interfaces. Importantly, skeletocutin E inhibits P. falciparum growth in both blood and liver stages, with IC values of 3.56 {+/-} 0.50 {micro}M in red blood cells and 3.70 {+/-} 0.74 {micro}M in primary human hepatocytes. Together, these findings establish PfPyrKII as a druggable antimalarial target and identify skeletocutin E as a promising lead compound for the rational development of dual-stage antimalarial therapies.

microbiology↗

bioRxiv2019

A New Ultradian Rhythm Linked to Protein Degradation and Synthesis in Mammalian Cells

We describe a new ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the individual histories of the dry mass of thousands of live cells simultaneously, each at a resolution of five minutes. Importantly, the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias. The rhythm is independent of circadian rhythm, has a period of 4 hours and is temperature-compensated. We demonstrated that the 4 hr rhythm is suppressed by proteostasis disruptors and is detected only in proliferating cells, suggesting that it represents the periodic dynamics of protein mass in growing cells. Brief teaserWe have revealed a 4 hr rhythm in cell dry mass dynamics that seems to be general in proliferating mammalian cells.

cell biology↗

bioRxiv2018

Confinement-induced transition between wave-like collective cell migration modes

The structural and functional organization of biological tissues relies on the intricate interplay between chemical and mechanical signaling. Whereas the role of constant and transient mechanical perturbations is generally accepted, several studies recently highlighted the existence of long-range mechanical excitations (i.e., waves) at the supracellular level. Here, we confine epithelial cell mono-layers to quasi-one dimensional geometries, to force the establishment of tissue-level waves of well-defined wavelength and period. Numerical simulations based on a self-propelled Voronoi model reproduce the observed waves and exhibit a phase transition between a global and a multi-nodal wave, controlled by the confinement size. We confirm experimentally the existence of such a phase transition, and show that wavelength and period are independent of the confinement length. Together, these results demonstrate the intrinsic origin of tissue oscillations, which could provide cells with a mechanism to accurately measure distances at the supracellular level.

biophysics↗