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Updated: Nov 22, 2025

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From Transcript to Tissue: Multiscale Modeling from Cell Signaling to Matrix Remodeling.

Linda Irons1, Marcos Latorre2, Jay D Humphrey2

  • 1Department of Biomedical Engineering, Yale University, New Haven, CT, USA. linda.irons@yale.edu.

Annals of Biomedical Engineering
|January 8, 2021
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This study integrates cell signaling and vessel mechanics models to simulate aortic remodeling. The new model enhances understanding of how cell communication influences tissue structure and function.

Keywords:
Constrained mixturesGrowth and remodelingHomeostasisLogic-based modelingMechanobiology

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Area of Science:

  • Biomedical Engineering
  • Computational Biology
  • Physiology

Background:

  • Tissue biomechanics depend on cell signaling regulating matrix dynamics.
  • Existing models often use phenomenological relations for vessel remodeling.
  • A mechanistic understanding of cell signaling's role in tissue adaptation is needed.

Purpose of the Study:

  • To couple cell-level signaling and vessel-level growth models for multiscale simulation.
  • To mechanistically model aortic remodeling by replacing phenomenological relations with a signaling model.
  • To investigate the feedback between vascular mechanics and cell signaling.

Main Methods:

  • Coupled two modeling frameworks: vessel-level growth/remodeling and cell-level signaling.
  • Replaced phenomenological relations with a logic-based signaling model generating ODEs.
  • Simulated aortic remodeling, incorporating collagen synthesis, MMPs, and cell proliferation.

Main Results:

  • The coupled model predicts changes in vascular tissue in response to mechanical stress and Angiotensin II.
  • Model predictions were verified against hypertensive murine aortic data and existing models.
  • The approach accounts for signaling noise and cell population heterogeneity.

Conclusions:

  • The integrated model provides a mechanistic basis for understanding tissue homeostasis and adaptation.
  • This multiscale approach offers improved insights into vascular remodeling processes.
  • Cell signaling plays a critical role in mediating tissue-level biomechanical responses.