Biology subjects

Matejcic, M.

Publications and source records attributed to Matejcic, M..

4 recordsLinked to original sources

bioRxiv2025

Mechanical Coordination of Intestinal Cell Extrusion by Supracellular 3D Force Patterns

Every day, the mammalian intestinal epithelium extrudes millions of cells to sustain tissue self-renewal. Despite its fundamental role in intestinal homeostasis, the mechanisms that trigger, compartmentalize, and execute intestinal cell extrusion remain largely unknown. Here, using intestinal organoids, we map the three-dimensional forces and cytoskeletal dynamics that drive intestinal cell extrusion. We show that, unlike in other epithelia, extrusion is initiated by the sudden dissolution of a contractile myosin 2A meshwork triggered by a calcium influx. Following meshwork dissolution, the extruding cell and its neighbors generate an upwards traction force that requires myosin contractility but is generated by lamellipodial protrusions in neighboring cells. Importantly, these lamellipodia not only act as force generators but also determine whether extrusion occurs apically or basally, serving as symmetry breakers of the process. Finally, we show that compartmentalization of cell extrusion to the outside of the intestinal crypt does not require curvature and instead depends on myosin 2A. Our findings reveal that the intestinal epithelium exhibits a distinctive mode of extrusion, in which tension differentials--rather than compressive stresses from crowding--trigger and compartmentalize cell removal.

cell biology↗

bioRxiv2020

Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration

Intestinal organoids capture essential features of the intestinal epithelium such as folding of the crypt, spatial compartmentalization of different cell types, and cellular movements from crypt to villus-like domains. Each of these processes and their coordination in time and space requires patterned physical forces that are currently unknown. Here we map the three-dimensional cell-ECM and cell-cell forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the ECM and folds through apical constriction, whereas the transit amplifying zone pulls the ECM and elongates through basal constriction. Tension measurements establish that the transit amplifying zone isolates mechanically the stem cell compartment and the villus-like domain. A 3D vertex model shows that the shape and force distribution of the crypt can be largely explained by cell surface tensions following the measured apical and basal actomyosin density. Finally, we show that cells are pulled out of the crypt along a gradient of increasing tension, rather than pushed by a compressive stress downstream of mitotic pressure as previously assumed. Our study unveils how patterned forces enable folding and collective migration in the intestinal crypt.

cell biology↗

bioRxiv2019

Tissue shape determines actin-dependent nuclear migration mechanisms in neuroepithelia

Correct nuclear position is crucial for cellular function. Depending on cell context however, cytoskeletal elements and force generation mechanisms vary. While these mechanisms have been intensely studied in single cells, how nuclear positioning is linked to tissue morphology is less clear. Here, we compare apical nuclear positioning in developing straight and curved neuroepithelia of zebrafish. Interestingly, in differently shaped neuroepithelia the kinetics of nuclear positioning differ and we find that distinct actin-dependent mechanisms are employed. In straight neuroepithelia nuclear positioning is controlled by Rho-ROCK-dependent myosin contractility. Curved neuroepithelia use a formin-dependent pushing mechanism for which we propose a force generation theory. We suggest that cytoskeleton adaptability to tissue shape ensures correct nuclear positioning and robust epithelial maturation across different geometries. We further speculate that different mechanisms arise due to differences in actin arrangements during development, a theme highlighting the importance of developmental context for the execution of intracellular processes.

cell biology↗

bioRxiv2018

A non-cell autonomous actin redistribution enables isotropic retinal growth

Tissue shape is often established early in development and needs to be scaled isotropically during growth. However, the cellular contributors and ways in which cells interact inside tissues to enable coordinated isotropic tissue scaling are not yet understood. Here, we follow cell and tissue shape changes in the zebrafish retinal neuroepithelium, which forms a cup with a smooth surface early in development and maintains this architecture as it grows. By combining 3D analysis and theory, we show that a global increase in cell height is necessary to maintain this tissue shape during growth. Timely cell height increase is governed by non-cell autonomous actin redistribution. Blocking actin redistribution and cell height increase perturbs isotropic scaling and leads to disturbed, folded tissue shape. Taken together, our data show how global changes in cell shape enable isotropic growth of the developing retinal neuroepithelium, a concept that could also apply to other systems.

developmental biology↗