ArticleNature communications2025
Altered extracellular matrix structure and elevated stiffness in a brain organoid model for disease.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Coordinated neural progenitor adaptations contribute to primate neocortical downscaling.Science advances · 2026Article
- Reduced mechanical shear is associated with early cortical differentiation and GDNF-GFRA1/RET signalling in human brain organoids.Stem cells translational medicine · 2026Article
- Architects of the Developing Brain: Cytoskeleton-Organizing Molecules in Neurodevelopmental Disorders.Cells · 2026Review
- Mechanobiology of hippocampal neurogenesis: directing neural stem cell fate through physical cues.Frontiers in molecular neuroscience · 2026Review
- Pluripotent stem cells-based neural organoids for modelling human brain development and diseases.Cell & bioscience · 2025Review
- Multimodal mechanoregulation strategies towards tissue regeneration.Mechanobiology in medicine · 2025Review
- Mechanomedicine: Present state and future promise.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human dorsal forebrain organoids show differentiation-state-specific protein secretion.iScience · 2025Article
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15 authors.
Funding
Abstract
The viscoelastic properties of tissues influence their morphology and cellular behavior, yet little is known about changes in these properties during brain malformations. Lissencephaly, a severe cortical malformation caused by LIS1 mutations, results in a smooth cortex. Here, we show that human-derived brain organoids with LIS1 mutation exhibit increased stiffness compared to controls at multiple developmental stages. This stiffening correlates with abnormal extracellular matrix (ECM) expression and organization, as well as elevated water content, measured by diffusion-weighted MRI. Short-term MMP9 treatment reduces both stiffness and water diffusion levels to control values. Additionally, a computational microstructure mechanical model predicts mechanical changes based on ECM organization. These findings suggest that LIS1 plays a critical role in ECM regulation during brain development and that its mutation leads to significant viscoelastic alterations.
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