Using a Novel Microfabricated Model of the Alveolar-Capillary Barrier to Investigate the Effect of Matrix Structure on Atelectrauma

Sci Rep. 2017 Sep 14;7(1):11623. doi: 10.1038/s41598-017-12044-9.

Abstract

The alveolar-capillary barrier is composed of epithelial and endothelial cells interacting across a fibrous extracelluar matrix (ECM). Although remodeling of the ECM occurs during several lung disorders, it is not known how fiber structure and mechanics influences cell injury during cyclic airway reopening as occurs during mechanical ventilation (atelectrauma). We have developed a novel in vitro platform that mimics the micro/nano-scale architecture of the alveolar microenvironment and have used this system to investigate how ECM microstructural properties influence epithelial cell injury during airway reopening. In addition to epithelial-endothelial interactions, our platform accounts for the fibrous topography of the basal membrane and allows for easy modulation of fiber size/diameter, density and stiffness. Results indicate that fiber stiffness and topography significantly influence epithelial/endothelial barrier function where increased fiber stiffness/density resulted in altered cytoskeletal structure, increased tight junction (TJ) formation and reduced barrier permeability. However, cells on rigid/dense fibers were also more susceptible to injury during airway reopening. These results indicate that changes in the mechanics and architecture of the lung microenvironment can significantly alter cell function and injury and demonstrate the importance of implementing in vitro models that more closely resemble the natural conditions of the lung microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Alveolar Epithelial Cells / metabolism
  • Biomimetic Materials
  • Blood-Air Barrier / physiology*
  • Cells, Cultured
  • Cytoskeleton / metabolism
  • Endothelial Cells / metabolism
  • Extracellular Matrix / metabolism*
  • Humans
  • In Vitro Techniques*
  • Microtechnology* / instrumentation
  • Microtechnology* / methods
  • Pulmonary Atelectasis / etiology*
  • Pulmonary Atelectasis / metabolism*
  • Pulmonary Atelectasis / pathology
  • Tight Junctions

Substances

  • Actins