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The Proceedings of the American Thoracic Society 5:364-365 (2008)
© 2008 The American Thoracic Society
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Lung Fibroblast Behavior Is Tuned by Substrate Stiffness

Justin D. Mih1 and Daniel J. Tschumperlin1

1 Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Daniel J. Tschumperlin, Ph.D., 665 Huntington Ave., Boston, MA 02115. E-mail: dtschump{at}hsph.harvard.edu

The lung parenchyma is characterized by a shear modulus (resistance to shape change) that varies with transpulmonary pressure. The shear modulus of an individual alveolar wall is estimated to be 1,500 to 2,000 Pa (1), but aging and disease conditions such as pulmonary fibrosis can alter the local and/or global stiffness of the parenchyma. While other cell types have been shown to exhibit stiffness-dependent biological responses, it is not known what influence the mechanical microenvironment of the parenchyma exerts on structural cells of the lung.

To facilitate exploration of stiffness-dependent lung cell biology, we studied human fetal lung fibroblasts (HFL-1) grown in a 96-well format on the surface of polyacrylamide gels with shear moduli spanning 50 to 51,200 Pa in twofold increments. A heterobifunctional crosslinker was used to conjugate equal surface concentrations of collagen I to the polyacrylamide surface, allowing specification of the cell–matrix interaction at the gel surfaces. Over 24 hours, fibroblast proliferation, as assessed by bromodeoxyuridine incorporation, increased with increasing stiffness. Conversely, activation of caspase 3/7 (a marker of apoptosis) decreased with increasing stiffness. In both cases, cells responded most sensitively to changes in shear modulus in the 400 to 3,200 Pa range. These results suggest that changes in the stiffness of the lung parenchyma within a physiologically relevant range may alter the balance between fibroblast proliferation and death, with potential implications for lung remodeling and pulmonary fibrosis.

FOOTNOTES

Supported by NIH GM-073628 (to D.J.T.).

Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form November 13, 2007; accepted in final form November 16, 2007)

REFERENCES

  1. Cavalcante FS, Ito S, Brewer K, Sakai H, Alencar AM, Almeida MP, Andrade JS Jr, Majumdar A, Ingenito EP, Suki B. Mechanical interactions between collagen and proteoglycans: implications for the stability of lung tissue. J Appl Physiol 2005;98:672–679.[Abstract/Free Full Text]




This Article
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Right arrow Articles by Tschumperlin, D. J.

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