TABLE I.

Representative sample of in vitro platforms that replicate mechanical forces in the lungs.

References	Mechanical Stimuli	Disease	Cell type(s)	Model type	Force application method	Key metrics in response to force
Ressler et al.105	Compression	Asthma	Rat tracheal epithelial	Transwell	Air pressurization above culture	RNA coding for Egr-1, endothelin-1, TGF-β
Swartz et al.121	Compression	Asthma	Normal human bronchial epithelial and normal human lung fibroblast (CCL-186)	Transwell epithelium culture over fibroblasts	Air pressurization above culture	Quantitative production of collagen, fibronectin
Tschumperlin et al.132	Compression	Asthma	Normal human bronchial epithelial	Transwell	Air pressurization above culture	MAP kinase and herparin-binding epidermal growth factor (HB-EGF)
Bilek et al.10	Stress field, pressure gradient	VILI	Fetal rat pulmonary epithelial (CCL-149)	Parallel plate flow chamber	Air bubble propagation	Cell death (live/dead stain)
Chu et al.24	Compression	Asthma	Normal human bronchial epithelial	Transwell	Air pressurization above culture	Quantitative expression of epidermal growth factor receptor ligands HB-EGF, epiregulin, amphiregulin, TGF-β
Tarran et al.125	Shear stress	Cystic fibrosis	Primary human epithelial	Transwell	Phasic motion of culture	Adenosine triphosphate (ATP) release, periciliary layer thickness
Choe et al.23	Compression	Asthma	Human fetal lung fibroblast (CCL-186)	Tissue-engineered human airway wall	Dynamic lateral compressive strain	Deposition of types III and IV collagen, MMPs-2 and-9
Huh et al.61	Shear stress, pressure gradient	Pulmonary edema	Primary human small airway epithelial	Microfluidic chip	Liquid plug propagation and rupture	Cell death (live/dead stain)
Yalcin et al.142	Shear stress, pressure gradient	ARDS	Fetal rat pulmonary epithelial (CCL-149)	Height adjustable parallel plate flow chamber	Air bubble propagation	Cell death (live/dead stain)
Sidhaye et al.114	Shear stress	General	Normal human bronchial epithelial	Cell culture insert	Laminar fluid flow	Paracellular permeability
Fronius et al.41	Shear stress	Cystic fibrosis	Xenopus oocyte	Xenopus oocyte	Fluid stream	Epithelial sodium channel activation
Huh et al.63	Strain	General	Human pulmonary microvascular endothelial and alveolar epithelial, peripheral neutrophil (H441, A549, E10)	Microfluidic chip	Stretching porous membrane	ICAM-1 (endothelium), ROS generation (epithelium), nanoparticle translocation
Douville et al.32	Shear stress, strain	ARDS	Human alveolar basal epithelial (A549) and primary murine alveolar epithelial	Microfluidic chip with flexible membrane	Membrane stretch and air-liquid interface oscillation	Cell death (live/dead stain)
Jacob and Gaver69	Stress field, pressure gradient	ARDS	Human pulmonary epithelial (H441)	Parallel plate flow chamber	Air bubble propagation	Paracellular permeability; Distribution of tight junction proteins ZO-1 and claudin 4
Stucki et al.119	Strain	General	Bronchial epithelial (16HBE14o−), primary human pulmonary alveolar epithelial, HUVEC	Microfluidic chip	Microdiaphragm stretching	Proliferation, IL-8 secretion
Manuyakorn et al.79	Strain	Asthma	Primary bronchial fibroblasts	Flexible silastic membranes	Cyclic strain	Proteoglycans, αSMA, collagens I and III, MMPs 2 & 8, IL-8
Song et al.117	Shear stress, pressure gradient	Obstructive lung diseases	Primary human small airway epithelial (CC-2547)	Microfluidic chip	Liquid plug propagation	Cell viability, NF-κB, stress fibers