Basement membrane mechanics drives patterned response to developmental signalling

Raffaelli A, Wyatt TP, Simon CS, Wenger LM, Niakan KK, Paluch EK, Kevin J Chalut
2026 · doi:10.64898/2026.02.13.705301
preprint OA: gold CC-BY-4.0
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⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-07-14 ⓘ

Basement membrane mechanics in human pluripotent stem cells and mouse embryos dictate spatiotemporal responses to developmental signaling, revealing a mechanochemical feedback mechanism crucial for pattern formation.

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⚙ AI-generated deep summary by qwen3.7-flash, 2026-08-27 · read from full text ⓘ

This study investigates how basement membrane mechanics regulate the spatiotemporal response to developmental signaling in human pluripotent stem cells and mouse embryos. The authors found that reducing mechanosensation through soft substrates or chemical inhibitors disrupts epithelial polarity and increases permeability, which abolishes stereotypical spatial patterning of BMP4-induced differentiation. In vivo experiments demonstrated that softening the basement membrane in mouse embryos triggers ectopic mesoderm differentiation, thereby disrupting normal gastrulation patterns. This paper is centrally about endometriosis — specifically, the competing interest statement identifies one of the authors as working for a company targeting this condition, linking the research context to women's health despite the basic science focus.

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Abstract

ABSTRACT Precise spatiotemporal patterning of cell fate decisions during development, such as those accompanying gastrulation, has traditionally been attributed to morphogen gradients. Emerging evidence also points to a crucial role for mechanics in regulating cell fate decisions. Here, we uncover that basement membrane mechanics in human pluripotent stem cells (hPSCs) regulates the spatiotemporal response to gastrulation-inducing BMP4. Reducing mechanosensation via soft substrates or chemical inhibitors abolishes stereotypical spatial patterning of the BMP4 response in hPSC colonies. This loss arises from disrupted epithelial polarity and increased permeability, which enhance BMP receptor accessibility. Strikingly, apical exposure to soluble laminin similarly disrupts polarity and suppresses hPSC mechanosensing, phenocopying the soft substrates effect and suggesting feedback between polarity signaling and mechanosensing. Finally, softening the basement membrane in mouse embryos triggers ectopic and premature mesoderm differentiation, disrupting gastrulation patterning. Together, this study describes a mechanochemical feedback mechanism that establishes basement membrane mechanics as a key regulator of developmental patterning.
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ABSTRACT Precise spatiotemporal patterning of cell fate decisions during development, such as those accompanying gastrulation, has traditionally been attributed to morphogen gradients. Emerging evidence also points to a crucial role for mechanics in regulating cell fate decisions. Here, we uncover that basement membrane mechanics in human pluripotent stem cells (hPSCs) regulates the spatiotemporal response to gastrulation-inducing BMP4. Reducing mechanosensation via soft substrates or chemical inhibitors abolishes stereotypical spatial patterning of the BMP4 response in hPSC colonies. This loss arises from disrupted epithelial polarity and increased permeability, which enhance BMP receptor accessibility. Strikingly, apical exposure to soluble laminin similarly disrupts polarity and suppresses hPSC mechanosensing, phenocopying the soft substrates effect and suggesting feedback between polarity signaling and mechanosensing. Finally, softening the basement membrane in mouse embryos triggers ectopic and premature mesoderm differentiation, disrupting gastrulation patterning. Together, this study describes a mechanochemical feedback mechanism that establishes basement membrane mechanics as a key regulator of developmental patterning. Competing Interest Statement T.P.J.W., L.M.D.W. and K.J.C all now work for Cyclana Bio, an early-stage women health company targeting endometriosis.

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europepmc
last seen: 2026-09-13T09:25:22.628771+00:00
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