A self-organized compression network arrests epithelial proliferation

Fuente: arXiv
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Main Authors: Daraf, Liav, Lavi, Yael, Saleem, Areej, Sanchez, Daniel Sevilla, Feldman, Yuri, Atia, Lior
Format: Preprint
Published: 2025
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author Daraf, Liav
Lavi, Yael
Saleem, Areej
Sanchez, Daniel Sevilla
Feldman, Yuri
Atia, Lior
author_facet Daraf, Liav
Lavi, Yael
Saleem, Areej
Sanchez, Daniel Sevilla
Feldman, Yuri
Atia, Lior
contents As epithelial development or wound closure approaches completion, cell proliferation progressively slows via contact inhibition of proliferation (CIP) - a mechanism understood as being strictly local. Here we report the discovery of inhibition of proliferation through an unanticipated mechanism that is non-local. As a confluent epithelial layer becomes progressively more jammed, two interpenetrating networks emerge: islands of mechanically compressed non-cycling cells percolating within an ocean of mechanically tensed cycling cells. The evolution of the compression network was found to be susceptible to both specific molecular stimulus and to injury-induced unjamming. Yet, in all circumstances, the size of compressed islands followed a power-law distribution that was well-captured by preferential network theory. Together, these findings demonstrate the existence of a network-based inhibition of proliferation (NIP) that is self-organizing and poised in proximity to criticality.
format Preprint
id arxiv_https___arxiv_org_abs_2509_16661
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle A self-organized compression network arrests epithelial proliferation
Daraf, Liav
Lavi, Yael
Saleem, Areej
Sanchez, Daniel Sevilla
Feldman, Yuri
Atia, Lior
Cell Behavior
Soft Condensed Matter
Adaptation and Self-Organizing Systems
Biological Physics
Tissues and Organs
As epithelial development or wound closure approaches completion, cell proliferation progressively slows via contact inhibition of proliferation (CIP) - a mechanism understood as being strictly local. Here we report the discovery of inhibition of proliferation through an unanticipated mechanism that is non-local. As a confluent epithelial layer becomes progressively more jammed, two interpenetrating networks emerge: islands of mechanically compressed non-cycling cells percolating within an ocean of mechanically tensed cycling cells. The evolution of the compression network was found to be susceptible to both specific molecular stimulus and to injury-induced unjamming. Yet, in all circumstances, the size of compressed islands followed a power-law distribution that was well-captured by preferential network theory. Together, these findings demonstrate the existence of a network-based inhibition of proliferation (NIP) that is self-organizing and poised in proximity to criticality.
title A self-organized compression network arrests epithelial proliferation
topic Cell Behavior
Soft Condensed Matter
Adaptation and Self-Organizing Systems
Biological Physics
Tissues and Organs
url https://arxiv.org/abs/2509.16661