Abstract

Fibrotic diseases are characterized by progressive and often irreversible scarring of connective tissue in various organs, leading to substantial changes in tissue mechanics largely as a result of alterations in collagen structure. This is particularly important in the lung because its bulk modulus is so critical to the volume changes that take place during breathing. Nevertheless, it remains unclear how fibrotic abnormalities in the mechanical properties of pulmonary connective tissue can be linked to the stiffening of its individual collagen fibers. To address this question, we developed a network model of randomly oriented collagen and elastin fibers to represent pulmonary alveolar wall tissue. We show that the stress–strain behavior of this model arises via the interactions of collagen and elastin fiber networks and is critically dependent on the relative fiber stiffnesses of the individual collagen and elastin fibers themselves. We also show that the progression from linear to nonlinear stress–strain behavior of the model is associated with the percolation of stress across the collagen fiber network, but that the location of the percolation threshold is influenced by the waviness of collagen fibers.

Highlights

  • Fibrotic diseases are characterized by progressive and often irreversible scarring of connective tissue in various organs, leading to substantial changes in tissue mechanics largely as a result of alterations in collagen structure

  • Networks of collagen and elastin in alveolar walls are random, web-like, and i­sotropic[6]. They produce nonlinear stress–strain behavior such that alveolar walls demonstrate an exponential increase in stress with increasing ­strain[7]

  • We present a computational model of the alveolar wall comprised of networks of randomly oriented collagen and elastin fibers coupled via a tunable degree of inter-network cross-linking

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Summary

Introduction

Fibrotic diseases are characterized by progressive and often irreversible scarring of connective tissue in various organs, leading to substantial changes in tissue mechanics largely as a result of alterations in collagen structure This is important in the lung because its bulk modulus is so critical to the volume changes that take place during breathing. It remains unclear how fibrotic abnormalities in the mechanical properties of pulmonary connective tissue can be linked to the stiffening of its individual collagen fibers. Determine how the bulk stress–strain behavior of the alveolar wall arises as an emergent consequence of percolation across the collagen network under the modulating influence of the fiber waviness

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