A Biomimetic, Copolymeric Membrane for Cell-Stretch Experiments with Pulmonary Epithelial Cells at the Air-Liquid Interface

Research output: Contribution to journalArticle

Abstract

Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(ε-)caprolactone and gelatin with tunable properties, resembling the main characteristics of the alveolar basement membrane is introduced. The thin bioinspired membrane (0.5 μm) is stretchable (up to 25% linear strain) with appropriate surface wettability and porosity for culturing lung epithelial cells under air–liquid interface conditions. The unique biphasic concept of this membrane provides optimum characteristics for initial cell growth (phase I) and then switch to biomimetic properties for cyclic cell-stretch experiments (phase II). It is showed that physiologic cyclic mechanical stretch improves formation of F-actin cytoskeleton filaments and tight junctions while non-physiologic over-stretch induces cell apoptosis, activates inflammatory response (IL-8), and impairs epithelial barrier integrity. It is also demonstrated that cyclic physiologic stretch can enhance the cellular uptake of nanoparticles. Since this membrane offers considerable advantages over currently used membranes, it may lead the way to more biomimetic in vitro models of the lung for translation of in vitro response studies into clinical outcome.

Details

Authors
  • Ali Doryab
  • Mehmet Berat Taskin
  • Philipp Stahlhut
  • Andreas Schröppel
  • Darcy E. Wagner
  • Jürgen Groll
  • Otmar Schmid
Organisations
External organisations
  • German Center for Lung Research (DZL)
  • Helmholtz Zentrum München
  • Julius Maximilian University of Würzburg
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Respiratory Medicine and Allergy

Keywords

  • alveolar-capillary barrier, cyclic mechanical stretch, hybrid polymers, in vitro cell-stretch model, tunable ultra-thin biphasic membrane
Original languageEnglish
Article number2004707
JournalAdvanced Functional Materials
Volume31
Issue number10
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes