Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development.

TitleMicrofluidic chest cavities reveal that transmural pressure controls the rate of lung development.
Publication TypeJournal Article
Year of Publication2017
AuthorsNelson, CM, Gleghorn, JP, Pang, M-F, Jaslove, JM, Goodwin, K, Varner, VD, Miller, E, Radisky, DC, Stone, HA
JournalDevelopment
Volume144
Issue23
Pagination4328-4335
Date Published2017 12 01
ISSN1477-9129
KeywordsAnimals, Biomechanical Phenomena, Female, Lung, Mice, Microfluidics, Models, Biological, Muscle Contraction, Muscle, Smooth, Organogenesis, Pregnancy, Pressure, Stress, Mechanical, Thoracic Cavity
Abstract

<p>Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissue types present within a developing organ remains unclear. Here, we use bioengineered 'microfluidic chest cavities' to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis, the frequency of airway smooth muscle contraction, and the rate of developmental maturation of the lungs, as assessed by transcriptional analyses. Time-lapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between different tissues to control the development of the embryonic lung.</p>

DOI10.1242/dev.154823
Alternate JournalDevelopment
PubMed ID29084801
PubMed Central IDPMC5769635
Grant ListR21 HL110335 / HL / NHLBI NIH HHS / United States
F30 HL139039 / HL / NHLBI NIH HHS / United States
R21 HL118532 / HL / NHLBI NIH HHS / United States
R01 GM083997 / GM / NIGMS NIH HHS / United States
R01 HL120142 / HL / NHLBI NIH HHS / United States