Biology subjects

Henkes, S.

Publications and source records attributed to Henkes, S..

4 recordsLinked to original sources

bioRxiv2025

Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties

For tissues to spread, they must be deformable while maintaining their structural integrity. How these opposing requirements are balanced within spreading tissues is not yet well understood. Here, we show that keratin intermediate filaments function in epithelial spreading by adapting tissue mechanical resilience to the stresses arising in the tissue during the spreading process. By analysing the expansion of the enveloping cell layer (EVL) over the large yolk cell in early zebrafish embryos in vivo, we found that keratin network maturation in EVL cells is promoted by stresses building up within the spreading tissue. Through genetic interference and tissue rheology experiments, complemented by a vertex model with mechanochemical feedback, we demonstrate that stress-induced keratin network maturation in the EVL increases tissue viscosity, which is essential for preventing tissue rupture. Interestingly, keratins are also required in the yolk cell for mechanosensitive actomyosin network contraction and flow, the force-generating processes pulling the EVL. These dual mechanosensitive functions of keratins enable a balance between pulling force production in the yolk cell and the mechanical resilience of the EVL against stresses generated by these pulling forces, thereby ensuring uniform and robust tissue spreading.

developmental biology↗

bioRxiv2024

Spiral-eyes: A soft active matter model of in vivo corneal epithelial cell migration

The mammalian cornea constantly regenerates its outer epithelial layer. Cells lost by abrasion are replaced by division of both corneal epithelial cells and stem cell populations around the corneal periphery, the limbus. Limbal-derived epithelial cells migrate into the cornea, maintaining equal rates of cell loss and replacement (the XYZ hypothesis). This process produces a striking stable spiral cell motion pattern across the corneal surface, with a central vortex. Here, we show that this spiral pattern can be explained by the interplay of limbus position, cell division, extrusion, and collective cell migration along the curved corneal surface. Using dissected LacZ mosaic murine corneas, we inferred the surface flow field by following stripe edges, revealing a tightening spiral. To explain these flow fields, we developed a cell-level in silico model treating corneal epithelial cells as soft, self-propelled particles with density-dependent proliferation and extrusion rates, and noisy alignment of migration direction. Even without global guidance cues, the model predicted stripes and spirals closely recapitulating experiment. A complementary continuum description generalised the XYZ hypothesis. Spiral formation was robust to curvature changes, but not topology, and sensitive to limbal stem cells and flocking alignment, showing how swarm physics on curved surfaces can explain tissue-scale biological processes.

biophysics↗

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↗

bioRxiv2016

Active Vertex Model for Cell-Resolution Description of Epithelial Tissue Mechanics

We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.

biophysics↗