For the science, see our Tweetorial 🧵: bsky.app/profile/iber...
Kudos to the @ethz.ch Animal Facility for championing transparency! 🙏
#3Rs #AnimalWelfare #LungDevelopment #COPD
Posts by Dagmar Iber & CoBi
We're fully committed to 3Rs:
♻️ Replace – comp models & simulations go beyond what animal data alone could reveal
📉 Reduce – just 7 pregnant females (severity degree 0) & reuse of 20-year-old datasets instead of new experiments
🔬 Refine – SkelePlex & our pipeline extract max insight from min data
The @ethz.ch Animal Facility featured our work on how the lung gets its energy-efficient shape and how it remodels in disease like COPD 🐭🫁 — as part of their spotlight on responsible animal research. 🧵(1/4)
Many processes influence boundary sharpness and placement: gene regulatory interactions, spatial averaging, cell sorting to name a few.
Our analysis shows that cellular readout noise is the main determinant of boundary sharpness, i.e. #TZW.
Preprint: doi.org/10.64898/202...
🧵 6/6
By matching simulations with measurement of #TZW & #positional #error, we inferred kinetic and readout noise levels - and found them in the reported range.
This further supports that reliable long-range morphogen patterning is feasible with physiological noise levels:
x.com/DagmarIber/s...
🧵 5/6
We uncover a trade-off regarding cell size:
• Larger cells yield sharper boundaries (smaller #TZW)
• Smaller cells reduce variability in boundary position between embryos (lower positional error)
The measured cell size in the neural tube perfectly balances boundary sharpness and precision.
🧵 4/6
Our theoretical & computational analysis shows that #TZW is primarily set by #noise in the #cellular #readout process, not by fluctuations in the morphogen gradient itself.
For exponential gradients, a noisy readout threshold naturally yields a position-independent TZW.
🧵 3/6
According to prevailing theory, transition zones should widen exponentially with distance from the morphogen source, due to stochastic effects at low morphogen copy numbers.
#Contrary, we find that #TZW remains about #constant, independent of readout position and developmental timepoint.
🧵 2/6
What determines the sharpness of cell fate boundaries in gradient-based patterning?
We quantified #transition #zone #widths (TZW) across seven progenitor domain boundaries spanning the entire dorsal-ventral axis of the developing #mouse #neural #tube.
Preprint: doi.org/10.64898/202...
🧵 1/6
Many processes influence boundary sharpness and placement: gene regulatory interactions, spatial averaging, cell sorting to name a few.
Our analysis shows that cellular readout noise is the main determinant of boundary sharpness, i.e. #TZW.
Preprint: doi.org/10.64898/202...
🧵 6/6
By matching simulations with measurement of #TZW & #positional #error, we inferred kinetic and readout noise levels - and found them in the reported range.
This further supports that reliable long-range morphogen patterning is feasible with physiological noise levels:
x.com/DagmarIber/s...
🧵 5/6
Paper & poster are available on the COMSOL conference website: www.comsol.com/paper/direct...
"Within the competition to bring this field to a new level, SimuCell3D is remarkable and will mark a clear evolution of the topic."
🥁That’s what the committee said about this #SIBRemarkableOutputs 2024
👉Discover the output: tinyurl.com/53arz2rz
@iberd.bsky.social
The goal: make it easier for others to reproduce and extend these models within COMSOL.
We hope this serves as a generalizable reference for simulating collective cell behavior and pattern formation.
arxiv.org/pdf/2509.08930
This complements our earlier work introducing the DCM model 👉 bsky.app/profile/iber...
That previous paper focused on the biological questions and mathematical framework.
Here, we focus on the practical COMSOL #PIDE implementation: setup, BCs, 1D–3D, and Lagrangian reformulation for growth.
Out now: Simulating Organogenesis in #COMSOL: Tissue Patterning with Directed Cell Migration
We provide a detailed walkthrough of how to implement #DCM partial integro-differential equation models - enabling accessible simulations of tissue patterning and morphogenesis.
arxiv.org/pdf/2509.08930
Our paper "Morphogen gradients can convey position and time in growing tissues" is now out in Newton @cp-newton.bsky.social
Quite fitting to see this novel idea that morphogen gradients not only encode position, but can also time & synchronise development over long distances out in a new journal.
📄 Read the full study here: doi.org/10.1101/2025...
🎯 Useful for: developmental biology, tissue engineering, pattern formation, and computational modeling
#DevBio #PatternFormation #CellMigration #Morphogenesis #ComputationalBiology
📌 Summary:
• #DCM is a rapid, robust mechanism for developmental pattern formation
• COMSOL FEM implementation makes DCM models numerically accessible
• #DCM patterning parameter ranges and timeframes
• Pattern Orientation via attraction anisotropy or directed tissue growth
👇Thread 🧵(10/11)
2. Dynamic #attraction #zones
Spatially varying cell attraction that changes with tissue growth can guide migrating cells, leading to precise large-scale patterning.
This mimics how tissues form rings, bands, or layered structures in vivo.
👇Thread 🧵(9/11)
We identify two mechanisms for guiding pattern orientation:
1. #Anisotropic #attraction
Cells pulling or migrating more strongly in one direction form aligned stripe-like patterns—e.g., during directional tissue growth.
👇Thread 🧵(8/11)
#DCM naturally leads to unoriented patterns—spots, labyrinths—similar to Turing-like systems.
But biological tissues often require oriented patterns to fulfill specific functions.
Can DCM produce stripes, too?
👇Thread 🧵(7/11)
Three key parameters drive the emergence and morphology of patterns:
• Initial density of motile cells
• Intercellular attraction strength
• Cell sensing radius
👇Thread 🧵(6/11)
Simulations and linear stability analysis allowed us to find #critical #conditions for pattern formation and predict #patterning #speed.
We show under which conditions #DCM can realistically pattern tissues in development.
👇Thread 🧵(5/11)
We developed a mathematical framework that represents a wide range of #DCM cues, e.g., chemotaxis, durotaxis, haptotaxis & a general Finite Element Method #FEM:
👉 1D, 2D, 3D
👉 arbitrary geometries & boundary conditions
👉 isotropic & anisotropic interactions
👉 fast, large-scale simulations
🧵(4/11)
To study #DCM, both discrete and continuum models have been used.
But:
👉 Discrete models are computationally expensive.
👉 Continuum models have required custom Finite Volume Method #FVM implementations—until now.
👇Thread 🧵(3/11)
During embryonic development, cellular tissues transition from uniform starting conditions into robust spatial patterns.
#DCM offers a particularly fast and versatile route to spontaneously symmetry breaks and pattern formation without tissue buckling.
🧵(2/11)