Myofibroblasts slow down defect recombination dynamics in mixed cell monolayers

Fuente: arXiv
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Main Authors: Zheng, Zhaofei, Luo, Yuxin, Chen, Juan, Luo, Yimin
Format: Preprint
Published: 2025
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author Zheng, Zhaofei
Luo, Yuxin
Chen, Juan
Luo, Yimin
author_facet Zheng, Zhaofei
Luo, Yuxin
Chen, Juan
Luo, Yimin
contents Cellular organization and mechanotransduction pathways are crucial regulators of tissue morphogenesis, whereas their dysregulation contributes to pathologies. Overactive myofibroblasts are key drivers of fibrosis, yet how their presence alters collective cellular ordering remains unclear. Owing to steric interactions, elongated cells exhibit local order. Topological defects, where alignment is disrupted, have been postulated to serve as mechanical centers. In this study, we examine how incorporating slower moving myofibroblast phenotype impacts defect relaxation in monolayers consisting of co-cultured fibroblasts and myofibroblasts. In this system, myofibroblasts act as the less active component. Increasing their fraction increases disorder strength and slows defect recombination. On microgrooved surfaces, higher myofibroblast concentrations lead to worse alignment, suggesting single-cell mechanosensing and cell-cell interactions act jointly. Furthermore, we found that myofibroblasts preferentially localize at negatively charged -1/2 defects, whereas fibroblasts localize at +1/2 defects. Consequently, the slowdown of recombination dynamics can be partially attributed to myofibroblasts' preferential association with the less mobile -1/2 defects, increasing local friction and impeding defect mobility. This localization may also reduce compressive stress on myofibroblasts, as indicated by immunofluorescence of a downstream mechanotransducer. This work provides insights into possible connections between topological defects and cell motility in mixed phenotype monolayers.
format Preprint
id arxiv_https___arxiv_org_abs_2512_22923
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Myofibroblasts slow down defect recombination dynamics in mixed cell monolayers
Zheng, Zhaofei
Luo, Yuxin
Chen, Juan
Luo, Yimin
Soft Condensed Matter
Biological Physics
Cellular organization and mechanotransduction pathways are crucial regulators of tissue morphogenesis, whereas their dysregulation contributes to pathologies. Overactive myofibroblasts are key drivers of fibrosis, yet how their presence alters collective cellular ordering remains unclear. Owing to steric interactions, elongated cells exhibit local order. Topological defects, where alignment is disrupted, have been postulated to serve as mechanical centers. In this study, we examine how incorporating slower moving myofibroblast phenotype impacts defect relaxation in monolayers consisting of co-cultured fibroblasts and myofibroblasts. In this system, myofibroblasts act as the less active component. Increasing their fraction increases disorder strength and slows defect recombination. On microgrooved surfaces, higher myofibroblast concentrations lead to worse alignment, suggesting single-cell mechanosensing and cell-cell interactions act jointly. Furthermore, we found that myofibroblasts preferentially localize at negatively charged -1/2 defects, whereas fibroblasts localize at +1/2 defects. Consequently, the slowdown of recombination dynamics can be partially attributed to myofibroblasts' preferential association with the less mobile -1/2 defects, increasing local friction and impeding defect mobility. This localization may also reduce compressive stress on myofibroblasts, as indicated by immunofluorescence of a downstream mechanotransducer. This work provides insights into possible connections between topological defects and cell motility in mixed phenotype monolayers.
title Myofibroblasts slow down defect recombination dynamics in mixed cell monolayers
topic Soft Condensed Matter
Biological Physics
url https://arxiv.org/abs/2512.22923