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Mechanical Regulation of Bronchospasm: A Lung-on-Chip Model of AsthmaThursday, 9 July 2015 at 12:00  Add to Calendar ▼2015-07-09 12:00:002015-07-09 13:00:00Europe/LondonMechanical Regulation of Bronchospasm: A Lung-on-Chip Model of AsthmaSELECTBIOenquiries@selectbiosciences.comThis study presents a lung-on-chip platform that allows biomechanical studies of bronchoconstriction and asthma. The PDMS-based device consists of a human airway epithelial layer in an air-liquid interface, and a human airway smooth-muscle layer, separated by a perforated membrane. A pressure gradient is introduced to the upper layer of the lung chip, so that epithelial cells experience compressive stresses similar to physiological levels encountered during bronchospasms. To measure the biomechanical effects of the secretions caused by this compressive stress on smooth-muscle cells, contraction or relaxation in the smooth-muscle layer is measured using magnetic beads introduced into the bottom layer of the chip. Absolute and relative stiffness and their change over time is then quantified using optical magnetic-twisting cytometry. The results show that compressive stress applied on the epithelial layer leads to strong contraction in the smooth muscle layer, with more than two-fold change in average stiffness within two minutes. The study further shows that mechanical stresses on the epithelial cells activate the mechanosensor and transcriptional regulator YAP, which differentially activates COX1 and COX2, leading to secretions that contract smooth-muscle cells. The results indicate that short term effects of compressed epithelial cells on smooth-muscle cells may reinforce bronchoconstriction through positive feedback. |
Add to Calendar ▼2015-07-08 00:00:002015-07-09 00:00:00Europe/LondonOrgan-on-a-Chip ConferenceSELECTBIOenquiries@selectbiosciences.com
