Biology subjects

Sknepnek, R.

Publications and source records attributed to Sknepnek, R..

6 recordsLinked to original sources

bioRxiv2025

Quantifying the shape of cells - from Minkowski tensors to p-atic order

P-atic liquid crystal theories offer new perspectives on how cells self-organize and respond to mechanical cues. Understanding and quantifying the underlying orientational orders is therefore essential for unraveling the physical mechanisms that govern tissue dynamics. Due to the deformability of cells this requires quantifying their shape. We introduce rigorous mathematical tools and a reliable framework for such shape analysis. Applying this to segmented cells in MDCK monolayers and computational approaches for active vertex models and multiphase field models allows to demonstrate independence of shape measures and the presence of various p-atic orders at the same time. This challenges previous findings and opens new pathways for understanding the role of orientational symmetries and p-atic liquid crystal theories in tissue mechanics and development.

biophysics↗

bioRxiv2024

An active matter model captures the spatial dynamics of actomyosin oscillations during morphogenesis

The apicomedial actomyosin network is crucial for generating mechanical forces in cells. Oscillatory behaviour of this contractile network is commonly observed before or during significant morphogenetic events. For instance, during the development of the Drosophila adult abdominal epidermis, larval epithelial cells (LECs) undergo pulsed contractions before being replaced by histoblasts. These contractions involve the formation of contracted regions of concentrated actin and myosin. However, the emergence and control of pulsed contractions are not fully understood. Here, we combined in vivo 4D microscopy with numerical simulations of an active elastomer model applied to realistic cell geometries and boundary conditions to study LEC actomyosin dynamics. The active elastomer model was able to reproduce in vivo observations quantitatively. We also characterised the relationship between cell shape, cell polarity, and actomyosin network parameters with the spatiotemporal characteristics of the contractile network both in vivo and in simulations. Our results show that cell geometry, accompanied by boundary conditions which reflect the cells polarity, is essential to understand the dynamics of the apicomedial actomyosin network. Moreover, our findings support the notion that spatiotemporal oscillatory behaviour of the actomyosin network is an emergent property of the actomyosin network, rather than driven by upstream signalling.

biophysics↗

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↗

bioRxiv2019

Assemblies of F-actin and myosin-II minifilaments: steric hindrance and stratification at the membrane cortex

Recent in-vivo studies have revealed that several membrane proteins are driven to form nanoclusters by active contractile flows arising from F-actin and myosin at the cortex. The mechanism of clustering was shown to be arising from the dynamic patterning of transient contractile platforms (asters) generated by actin and myosin. Myosin-II, which assemble as minifilaments consisting of tens of myosin heads, are rather bulky structures and hence a concern could be that steric considerations might obstruct the emergence of nanoclustering. Here, using coarse-grained, agent-based simulations that respect the size of constituents, we find that in the presence of steric hindrance, the patterns exhibited by actomyosin in two dimensions, do not resemble the steady state patterns observed in our in-vitro reconstitution of actomyosin on a supported bilayer. We then perform simulations in a thin rectangular slab, allowing the separation of a layer of actin filaments from those of myosin-II minifilaments. This recapitulates the observed features of in-vitro patterning. Using super resolution microscopy, we find direct evidence for stratification in our in-vitro system. Our study suggests the possibility that molecular stratification may be an important organising feature of the cortical cytoskeleton in-vivo.

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↗

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↗