ORIGINAL RESEARCH article
Front. Netw. Physiol.
Sec. Networks in the Respiratory System
Volume 5 - 2025 | doi: 10.3389/fnetp.2025.1589216
This article is part of the Research TopicThe New Frontier of Network Physiology: From Temporal Dynamics to the Synchronization and Principles of Integration in Networks of Physiological Systems, Volume IIIView all 10 articles
Bifurcation in the Healing or Fibrotic Response in a Network Model of Fibrosis: Role of the Initial Injury Structure
Provisionally accepted- 1Biomedical Engineering, Boston University, Boston, MA, United States
- 2Mechanical Engineering, Boston University, Boston, MA, United States
- 3Vermont Lung Center, Larner College of Medicine, University of Vermont, Burlington, Vermont, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Pulmonary fibrosis (PF) is a heterogeneous progressive lung disease characterized by excessive extracellular matrix (ECM) deposi on and cross-linking, leading to irreversible ssue s ffening and loss of func on. Previous evidence suggests that percola on behavior, where increasing local s ffness facilitates the emergence of s ff regions that span the ssue, underlies the s ffening of the ECM, and drives irreversible mechanical dysfunc on. However, it is not fully understood how percola on emerges from the complex interac ons between cells and the ECM. In this study, we inves gated a previously published agent-based spring network model of PF that exhibited bifurca on behavior between healing and fully developed fibrosis as network members were gradually s ffened. By systema cally analyzing the configura on of the ini al ssue injury, we iden fy key structural determinants that govern whether an injury heals or transi ons into fibrosis. Results demonstrate that fibrosis is strongly associated with increased ini al clustering of injured springs, reduced inter-cluster distances, and the presence of cri cal s ffening sites that act as bifurca on points for disease progression. Furthermore, we show that selec vely modifying the s ffness of pivotal network regions at the me of injury can shi the network's trajectory from fibrosis to healing, highligh ng poten al interven on targets. These findings suggest that the network structure of ssue injury may serve as a predic ve marker for fibrosis suscep bility and provide a mechanis c basis for understanding the nonlinear progression of PF.
Keywords: Spring network, agent-based model, clustering, healing, Percolation
Received: 07 Mar 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Israel, Hall, Deng, Bates and Suki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Béla Suki, Biomedical Engineering, Boston University, Boston, 02215, MA, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.