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Biology subjects

Runser, S.

Publications and source records attributed to Runser, S..

3 recordsLinked to original sources

OptiCell3D: Precise inference of mechanical cell properties from microscopy imaging

We introduce OptiCell3D, an open-source image-based framework for inferring cellular mechanical properties directly from 3D microscopy data. By integrating short physical simulations with gradient-based optimization via backpropagation, our method substantially improves accuracy compared to existing approaches. Moreover, OptiCell3D enables mechanical inference in tissues that are too large to be fully imaged, extending its applicability to more complex biological systems. We demonstrate the power of our approach by applying OptiCell3D to five morphologically diverse mouse epithelial tissues. By combining inferred parameters with simulations and morphometric analysis, we find that the ratio of apical to lateral surface tension predicts cell aspect ratio across epithelial subtypes, linking a single mechanical parameter to the broad morphological diversity of epithelia. Finally, we apply our framework to stratified tissues, finding greater variability in pressure and surface tension between cells and tension gradients along the apico-basal axis.

biophysics↗

3D Simulation of Tissue Mechanics with Cell Polarization

The 3D organisation of cells determines tissue function and integrity, and changes dramatically in development and disease. Cell-based simulations have long been used to define the underlying mechanical principles. However, large computational costs have so far limited simulations to either simplified cell geometries or small tissue patches. Here, we present SimuCell3D, a highly efficient open-source program to simulate large tissues in 3D with subcellular resolution, growth, proliferation, extracellular matrix, fluid cavities, nuclei, and non-uniform mechanical properties, as found in polarised epithelia. Spheroids, vesicles, sheets, tubes, and other tissue geometries can readily be imported from microscopy images and simulated to infer biomechanical parameters. Doing so, we show that 3D cell shapes in layered and pseudostratified epithelia are largely governed by a competition between surface tension and intercellular adhesion. SimuCell3D enables the large-scale in silico study of 3D tissue organization in development and disease at an unprecedented level of detail.

bioinformatics↗

The Biomechanical Basis of Biased Epithelial Tube Elongation

During lung development, epithelial branches expand preferentially in longitudinal direction. This bias in outgrowth has been linked to a bias in cell shape and in the cell division plane. How this bias arises is unknown. Here, we show that biased epithelial outgrowth occurs independent of the surrounding mesenchyme, of preferential turn-over of the extracellular matrix at the bud tips, and of FGF signalling. There is also no evidence for actin-rich filopodia at the bud tips. Rather, we find epithelial tubes to be collapsed during early lung and kidney development, and we observe fluid flow in the narrow tubes. By simulating the measured fluid flow inside segmented narrow epithelial tubes, we show that the shear stress levels on the apical surface are sufficient to explain the reported bias in cell shape and outgrowth. We use a cell-based vertex model to confirm that apical shear forces, unlike constricting forces, can give rise to both the observed bias in cell shapes and tube elongation. We conclude that shear stress may be a more general driver of biased tube elongation beyond its established role in angiogenesis. Summary StatementWe systematically analysed the requirements for biased elongating outgrowth of epithelial tubes during lung and kidney development, and provide evidence that fluid-flow induced shear stress drives their biased elongation.

developmental biology↗