Prepatterned Tissue Stiffness Gradient Controls Organ shape and size
- 1New York University School of Medicine
Abstract
Organ morphogenesis is orchestrated by precise coupling of mechanical and biochemical signals, yet how these two signals are integrated within tissue niche to regulate organ shape and size remains poorly understood. Here, using sweat gland as a tractable model of exocrine mini-organs, we demonstrate that dermal fibroblasts play a key role to translate prepatterned tissue stiffness gradients into spatial Wnt5a gradients via Piezo1-mediated mechanosensing. Following epidermal placode formation, progenitor cells collectively invaginate into the dermis, where spatiotemporally graded Wnt5a directs their sequential transition from ductal to glandular fate in softer distal dermis, specifying distinct exocrine compartments. Perturbation of dermal stiffness gradients and mechanosensing in vivo and ex vivo alters Wnt5a expression levels and gradient patterns and thereby changes the ductal length and glandular size, revealing a direct link between tissue mechanics and organ dimensions. To recapitulate this process in vitro, we engineer a microfluidic platform capable of generating robust and linear morphogen gradients in 3D, allowing duct-to-gland fate transitions to occur at a high resolution. Together, our finding identifies prepatterned stiffness gradients as a master upstream regulator of coupled mechanical-biochemical signaling, define a mechanistic framework for two-step sequential glandular morphogenesis, and offer new strategies for engineering glandular epithelia in regenerative medicine.
Related
- CAF contractility controls collagen stiffness through history-dependent competition between mechanical and proteolytic remodeling
- Multilayer-assembled microfluidic chip with Tesla-valve channels: Combined biochemical gradient and mechanical stiffness interface for 3D SKOV3 cell culture
- Paired-surface spatial mechanomics links tissue stiffness maps to spatial transcriptomics
- WHEN MICROSCALE TRANSPORT CONTROLS MACROSCALE TISSUE FREEZING: A PARAMETRIC REGIME ANALYSIS
- Multiple sources array controls shear-wave field in soft tissue using time reversal
BibTeX
@misc{tong2026prepatterned,
title = {{Prepatterned Tissue Stiffness Gradient Controls Organ shape and size}},
author = {J. Tong and M.-J. Lin and N. Deng and M. Delliturri and M. Xu and S. E. Millar and M. Ito and H. Cai and C. P.-J. Lu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.748946},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.748946v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Prepatterned Tissue Stiffness Gradient Controls Organ shape and size
AU - J. Tong
AU - M.-J. Lin
AU - N. Deng
AU - M. Delliturri
AU - M. Xu
AU - S. E. Millar
AU - M. Ito
AU - H. Cai
AU - C. P.-J. Lu
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.748946
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.748946v1
AB - Organ morphogenesis is orchestrated by precise coupling of mechanical and biochemical signals, yet how these two signals are integrated within tissue niche to regulate organ shape and size remains poorly understood. Here, using sweat gland as a tractable model of exocrine mini-organs, we demonstrate that dermal fibroblasts play a key role to translate prepatterned tissue stiffness gradients into spatial Wnt5a gradients via Piezo1-mediated mechanosensing. Following epidermal placode formation, progenitor cells collectively invaginate into the dermis, where spatiotemporally graded Wnt5a directs their sequential transition from ductal to glandular fate in softer distal dermis, specifying distinct exocrine compartments. Perturbation of dermal stiffness gradients and mechanosensing in vivo and ex vivo alters Wnt5a expression levels and gradient patterns and thereby changes the ductal length and glandular size, revealing a direct link between tissue mechanics and organ dimensions. To recapitulate this process in vitro, we engineer a microfluidic platform capable of generating robust and linear morphogen gradients in 3D, allowing duct-to-gland fate transitions to occur at a high resolution. Together, our finding identifies prepatterned stiffness gradients as a master upstream regulator of coupled mechanical-biochemical signaling, define a mechanistic framework for two-step sequential glandular morphogenesis, and offer new strategies for engineering glandular epithelia in regenerative medicine.
ER -