Search bioRxiv⌕ Search

Biology subjects

Vagne, Q.

Publications and source records attributed to Vagne, Q..

5 recordsLinked to original sources

Analysis of 3D epithelial tissue packing reveals correlated patterns of cell height and skewing

Epithelia are tissues which envelop organs, exchange with and protect from their environment. The tight packing of cells within an epithelium guarantees its cohesiveness and impermeability, essential to its functions. Yet, how cells spatially arrange in three dimensions within an epithelium, and how the three-dimensional cell packing responds to geometrical constraints, is not fully understood. In a proliferating epithelium, cellular volumes vary from cell to cell, notably due to cell growth. At the same time, epithelia tend to display a smooth, continuous apical surface, indicating that cell shape determinants are spatially coupled. It is unclear how these and other factors modulate cell shape variability within the epithelium. Here, we segmented three-dimensional cell shapes of MDCK epithelia, grown in hollow spheres of alginate. With this assay, we could modulate the substrate adhesive properties, tissue curvature, and cell area density. We observed that as the tissue proliferates and cell density increases, average cell volume decreases. In contrast, cell height is relatively conserved over time, with an average value sensitive to the rigidity, curvature and adhesive strength of the substrate. We identified large and spatially correlated fluctuations in cell skewing, defined as the relative difference between apical and basal area that do not arise from curvature. Skewing is associated to spatial patterns of tilted cells whose apico-basal axis deviates from orthogonality to the substrate. Surprisingly, cell skewing and cell height are correlated, indicating internal rules for three-dimensional cell shapes. Altogether, our study identifies unexpected patterns of three-dimensional cell shape variation within a proliferative epithelium.

biophysics↗

Multiscale curvature modulates epithelial architecture and nuclear organization.

Curved geometries are a defining feature of epithelial tissues, yet how cells integrate curvature cues across spatial scales remains unclear. Here, we combined wavy hydrogels with inducible self-rolling substrates to readily and independently impose local and large-scale curvatures on epithelial monolayers, recapitulating key geometric features of bronchiolar epithelia. By controlling the orientation of local curvature relative to the large-scale curvature set by the tube axis, we show that multiscale curvature induces scale-dependent and anisotropic remodeling of cell shape, nuclear organization, and tissue thickness. In contrast, nuclei maintain a robust and conserved three-dimensional geometry, with curvature primarily regulating nuclear orientation rather than shape. This hierarchical induction of specific changes to the tissue architecture shows that multiscale curvature sensing is a fundamental physical principle governing epithelial architecture.

biophysics↗

Polarity-driven three-dimensional spontaneous rotation of a cell doublet

Cell mechanical interactions play a fundamental role in the self-organisation of organisms. How these interactions drive coordinated cell movement in three-dimensions remains unclear. Here we report that cell doublets embedded in a 3D extracellular matrix undergo spontaneous rotations and we investigate the rotation mechanism using live cell imaging, quantitative measurements, mechanical perturbations, and theory. We find that rotation is driven by a polarized distribution of myosin within cell cortices. The mismatched orientation of this polarized distribution breaks the doublet mirror symmetry. In addition, cells adhere at their interface through adherens junctions and with the extracellular matrix through focal contacts near myosin clusters. Using a physical theory describing the doublet as two interacting active surfaces, we find that rotation is driven by myosin-generated gradients of active tension, whose profiles are dictated by interacting cell polarity axes. We show that interface three-dimensional shapes can be understood from the Curie principle: shapes symmetries are related to broken symmetries of myosin distribution in cortices. To test for the rotation mechanism, we suppress myosin clusters using laser ablation and we generate new myosin clusters by optogenetics. Our work clarifies how polarity-oriented active mechanical forces drive collective cell motion in three dimensions.

biophysics↗

Glycan processing in the Golgi - optimal information coding and constraints on cisternal number and enzyme specificity

Many proteins that undergo sequential enzymatic modification in the Golgi cisternae are displayed at the plasma membrane as cell identity markers. The modified proteins, called glycans, represent a molecular code. The fidelity of this glycan code is measured by how accurately the glycan synthesis machinery realises the desired target glycan distribution for a particular cell type and niche. In this paper, we quantitatively analyse the tradeoffs between the number of cisternae and the number and specificity of enzymes, in order to synthesize a prescribed target glycan distribution of a certain complexity. We find that to synthesize complex distributions, such as those observed in real cells, one needs to have multiple cisternae and precise enzyme partitioning in the Golgi. Additionally, for fixed number of enzymes and cisternae, there is an optimal level of specificity of enzymes that achieves the target distribution with high fidelity. Our results show how the complexity of the target glycan distribution places functional constraints on the Golgi cisternal number and enzyme specificity.

biophysics↗

A Minimal Self-Organization model of the Golgi Apparatus

The design principles dictating the spatio-temporal organisation of eukaryotic cells, and in particular the mechanisms controlling the self-organisation and dynamics of membrane-bound organelles such as the Golgi apparatus, remain elusive. Although this organelle was discovered 120 years ago, such basic questions as whether vesicular transport through the Golgi occurs in an anterograde (from entry to exit) or retrograde fashion are still strongly debated. Here, we address these issues by studying a quantitative model of organelle dynamics that includes: de-novo compartment generation, inter-compartment vesicular exchange, and biochemical conversion of membrane components. We show that anterograde or retrograde vesicular transports are asymptotic behaviors of a much richer dynamical system. Indeed, the structure and composition of cellular compartments and the directionality of vesicular exchange are intimately linked. They are emergent properties that can be tuned by varying the relative rates of vesicle budding, fusion and biochemical conversion.Competing Interest StatementThe authors have declared no competing interest.View Full Text

biophysics↗