Steve Runser


Last Name

Runser

First Name

Steve

ORCID

0000-0002-6053-2784

Organisational unit

03791 - Iber, Dagmar / Iber, Dagmar

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2021 - 20257
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Publications 1 - 7 of 7
  • PolyHoop: Soft particle and tissue dynamics with topological transitions
    Item type: Journal Article
    Vetter, Roman; Runser, Steve; Iber, Dagmar (2024)
    Computer Physics Communications
    We present PolyHoop, a lightweight standalone C++ implementation of a mechanical model to simulate the dynamics of soft particles and cellular tissues in two dimensions. With only few geometrical and physical parameters, PolyHoop is capable of simulating a wide range of particulate soft matter systems: from biological cells and tissues to vesicles, bubbles, foams, emulsions, and other amorphous materials. The soft particles or cells are represented by continuously remodeling, non-convex, high-resolution polygons that can undergo growth, division, fusion, aggregation, and separation. With PolyHoop, a tissue or foam consisting of a million cells with high spatial resolution can be simulated on conventional laptop computers.
  • Morphometry and mechanical instability at the onset of epithelial bladder cancer
    Item type: Journal Article
    Lampart, Franziska L.; Vetter, Roman; Yamauchi, Kevin A.; et al. (2025)
    Nature Physics
    Malignancies of epithelial tissues, called carcinomas, account for most cancer cases. Research has largely focused on correlating different carcinoma subtypes to genetic alterations. However, as well as a rewiring in the signalling networks, carcinoma progression is accompanied by mechanical changes in the epithelial cells and the extracellular matrix. Here we reveal intricate morphologies in the basement membrane at the onset of bladder cancer and propose that they emerge from a mechanical instability upon epithelial overgrowth. We imaged mouse and human bladder tissue and performed differential growth simulations, and found that stiffness changes in the different mucosa layers can result in aberrant tissue morphologies. The resulting thickening, wrinkles and folds resemble early papillary tumours and carcinomas in situ. Atomic force microscopy confirmed local stiffness changes in the pathological basement membrane. Our findings suggest a possible mechanical origin of the different bladder carcinoma subtypes and may guide future developments in treatment and prophylaxis.
  • PolyHoop: Soft particle and tissue dynamics with topological transitions
    Item type: Working Paper
    Vetter, Roman; Runser, Steve; Iber, Dagmar (2023)
    arXiv
    We present PolyHoop, a lightweight standalone C++ implementation of a mechanical model to simulate the dynamics of soft particles and cellular tissues in two dimensions. With only few geometrical and physical parameters, PolyHoop is capable of simulating a wide range of particulate soft matter systems: from biological cells and tissues to vesicles, bubbles, foams, emulsions, and other amorphous materials. The soft particles or cells are represented by continuously remodeling, non-convex, high-resolution polygons that can undergo growth, division, fusion, aggregation, and separation. With PolyHoop, a tissue or foam consisting of a million cells with high spatial resolution can be simulated on conventional laptop computers.
  • Development and Application of Cell-Based Simulation Frameworks for Morphogenetic Problems
    Item type: Doctoral Thesis
    Runser, Steve (2025)
    Morphogenesis is the developmental process by which organisms acquire their shapes. This complex process relies on the dynamic interplay between mechanical forces and the diffusion of signaling molecules, which work together to guide cellular behaviors, ultimately leading to the formation of functional organs. Studying these dynamics experimentally in living embryos is challenging, given their fragile and inaccessible nature. Even when all factors influencing their growth are known, their combined effects can remain elusive. In this context, computer simulations serve as a valuable supplement to experimental methods, enabling the artificial reproduction of biological tissues. By manipulating the development of these virtual tissues, deeper insights can be gained into the mechanisms driving morphogenesis. Even though the complex shapes of cells as well as entities such as the extracellular matrix play pivotal roles during the morphogenesis of tissues, these features are often simplified or omitted in simulations due to the computational complexity and cost of modeling them accurately. This thesis aims to address this gap by developing new computational methods to accurately simulate cellular behaviors and estimate cellular properties during tissue morphogenesis. The first part of the thesis is concerned with the development of a novel high-resolution 2D model, named PolyHoop, capable of simulating soft particles such as biological cells, bubbles, and emulsions. The versatility of the designed model is showcased by simulating a wide range of phenomena. The numerical stability and efficiency of PolyHoop are then demonstrated by simulating the growth of a tissue from one to a million cells. The second part of this thesis discusses how the approach that underpins the efficiency and versatility of PolyHoop has been extended into three dimensions in a novel model called SimuCell3D. Similar to PolyHoop, SimuCell3D can simulate biological tissues at cellular resolution with high geometric fidelity. Its efficient implementation makes it several orders of magnitude faster than previously published implementations. First are presented the various features natively incorporated in SimuCell3D such as automatic cell surface polarization, organelles, or local mesh refinement. SimuCell3D is then applied to study the relationship between cell mechanical parameters and the architecture of a tissue as well as the shape of cells in pseudostratified tissues. The third part of this thesis discusses how a simplified version of SimuCell3D has been combined with a parameter optimization technique to infer the mechanical properties of cells in imaged tissues. This method, called OptiCell3D, uses short, fully differentiable simulations to determine the optimal combination of cell pressures and cortical tensions needed to keep a tissue in equilibrium. An extensive benchmark of this novel approach is performed to demonstrate its superior accuracy compared to previously published methods. The final part of the thesis is concerned with the study of the interactions between the different cell types of the developing pancreas. The gene expression profiles of isolated single cells are used to identify potential interactions between the major cell types of the pancreas. The devised analysis predicted a total of more than 40,000 potential interactions. Several of these predictions were experimentally validated, revealing previously unknown chemical signaling interactions that influence pancreatic morphogenesis. The identified interactions can now be integrated into the mechanical models developed in this thesis, enabling an accurate representation of both cell mechanics and chemical signaling during pancreatic morphogenesis.
  • The biomechanical basis of biased epithelial tube elongation in lung and kidney development
    Item type: Journal Article
    Conrad, Lisa; Runser, Steve; Gómez, Harold F.; et al. (2021)
    Development
    During lung development, epithelial branches expand preferentially in a 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 turnover 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.
  • 3D Simulation of Tissue Mechanics with Cell Polarization
    Item type: Working Paper
    Runser, Steve; Vetter, Roman; Iber, Dagmar (2023)
    bioRxiv
    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.
  • SimuCell3D: three-dimensional simulation of tissue mechanics with cell polarization
    Item type: Journal Article
    Runser, Steve; Vetter, Roman; Iber, Dagmar (2024)
    Nature Computational Science
    The three-dimensional (3D) organization of cells determines tissue function and integrity, and changes markedly in development and disease. Cell-based simulations have long been used to define the underlying mechanical principles. However, high computational costs have so far limited simulations to either simplified cell geometries or small tissue patches. Here, we present SimuCell3D, an efficient open-source program to simulate large tissues in three dimensions with subcellular resolution, growth, proliferation, extracellular matrix, fluid cavities, nuclei and non-uniform mechanical properties, as found in polarized 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 a great level of detail.
Publications 1 - 7 of 7