# A multi-scale computational model of the extracellular matrix of the lung

> **NIH NIH U01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $772,568

## Abstract

Cells create their own biochemical and mechanical environment, and at the same time are exquisitely sensitive
to it, displaying a non-equilibrium homeostatic state that ensures normal extracellular matrix (ECM) function
throughout life. There are two currently incurable lung diseases for which this maintenance fails. Emphysema
involves the progressive destruction of tissue with loss of ECM stiffness while pulmonary fibrosis is characterized
by tissue stiffening due to excessive ECM deposition. These are also chronic progressive diseases in which
inflammation, mechanotransduction and cellular migration destabilize local homeostatic control of the ECM. Our
overarching hypothesis is that abnormalities in the homeostatic feedback between ECM mechanics and cellular
responses are central to the pathophysiology of both emphysema and pulmonary fibrosis. The goal of this
proposal is to develop and test a multi-scale computational platform that will advance critical new insight into
how deterioration of homeostatic cell-ECM coupling leads to specific disease forms. Aim 1: Develop a multiscale
computational model of the lung parenchyma. The alveolar structure of the parenchyma will be represented
as a 3D network of elastic sheets. Autonomous agents will be used to represent various cell types, such as
fibroblasts and inflammatory cells, in the tissue. The agents adhering to rule sets defining their stochastic
migration and their secretion of inflammatory and enzymatic factors that remodel elastin and collagen will be
placed throughout the network. Agent movement and activity will be determined throughout time as the network
breathes. The physics-based and agent-based components of the model will be linked through the effects of
stress and strain on agent responses that maintain local ECM properties, which in turn determine the global
mechanics of the network. Aim 2: Determine the spatial and temporal distribution of ECM composition and
inflammation in rodent models of emphysema and pulmonary fibrosis. Emphysema and fibrosis will be induced
by cigarette smoke extract and bleomycin, respectively, in rats. The degree of correspondence between cell and
injury locations throughout the tissue will be determined and used to derive rules of behavior for the various cell
types for the agent-based model of Aim 1. Aim 3: Determine how macroscopic structure and parenchymal
mechanics evolve over time in rodent models of emphysema and pulmonary fibrosis. The structure on micro-CT
and the mechanical characteristics of the lungs in the animal models will be followed over time in order to
determine how ECM structure-function evolves with advancing pathology, and to validate the physics-based
ECM network model in Aim 1. Aim 4: Predict tissue structure and function during the evolution of emphysema
and pulmonary fibrosis. The model of Aim 1 will be initialized away from the homeostatic state, allowed to evolve
over time and its structure and function compared to experimental ...

## Key facts

- **NIH application ID:** 10187641
- **Project number:** 5U01HL139466-04
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** BELA SUKI
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $772,568
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187641

## Citation

> US National Institutes of Health, RePORTER application 10187641, A multi-scale computational model of the extracellular matrix of the lung (5U01HL139466-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10187641. Licensed CC0.

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