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Updated: Aug 8, 2025

An Experimental System to Study Mechanotransduction in Fetal Lung Cells
Published on: February 16, 2012
Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate
Kazushige Shiraishi1, Parisha P Shah2, Michael P Morley3
1Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
Lungs undergo mechanical strain during breathing, but how these biophysical forces affect cell fate and tissue homeostasis are unclear. We show that biophysical forces through normal respiratory motion actively maintain alveolar type 1 (AT1) cell identity and restrict these cells from reprogramming into AT2 cells in the adult lung. AT1 cell fate is maintained at homeostasis by Cdc42- and Ptk2-mediated actin remodeling and cytoskeletal strain, and inactivation of these pathways causes a rapid reprogramming into the AT2 cell fate. This plasticity induces chromatin reorganization and changes in nuclear lamina-chromatin interactions, which can discriminate AT1 and AT2 cell identity. Unloading the biophysical forces of breathing movements leads to AT1-AT2 cell reprogramming, revealing that normal respiration is essential to maintain alveolar epithelial cell fate. These data demonstrate the integral function of mechanotransduction in maintaining lung cell fate and identifies the AT1 cell as an important mechanosensor in the alveolar niche.
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