A network model of correlated growth of tissue stiffening in pulmonary fibrosis

Abstract

During the progression of pulmonary fibrosis, initially isolated regions of high stiffness form and grow in the lung tissue due to collagen deposition by fibroblast cells. We have previously shown that ongoing collagen deposition may not lead to significant increases in the bulk modulus of the lung until these local remodeled regions have become sufficiently numerous and extensive to percolate in a continuous path across the entire tissue [Bates {\it et al.} 2007 {\it Am. J. Respir. Crit. Care Med.} {\bf 176} 617]. In the present study, we investigate whether spatial correlations influence the bulk modulus in a two-dimensional elastic network model of lung tissue. Random collagen deposition at a single site is modeled by increasing the elastic constant of the spring at that site by a factor of 100. By contrast, correlated collagen deposition is represented by stiffening the springs encountered along a random walk starting from some initial spring, the rationale being that excess collagen deposition is more likely in the vicinity of an already stiff region. A combination of random and correlated deposition is modeled by performing random walks of length $N$ from randomly selected initial sites, the balance between the two processes being determined by $N$. We found that the dependence of bulk modulus, $B(N,c)$, on both $N$ and the fraction of stiff springs, $c$, can be described by a strikingly simple set of empirical equations. Our results suggest that the spatial correlation of collagen deposition in the fibrotic lung has a strong effect on the rate of lung function decline and on the mechanical environment in which the cells responsible for remodeling find themselves.