title: Interstitial fluid flow of alveolar primary septa after pneumonectomy.
abstract: Neoalveolation is known to occur in the remaining lung after pneumonectomy. While compensatory lung growth is a complex process, stretching of the lung tissue appears to be crucial for tissue remodeling. Even a minute shear stress exerted on fibroblasts in the interstitial space is known to trigger cell differentiation into myofibroblast that are essential to building new tissues. We hypothesize that the non-uniform motion of the primary septa due to their heterogeneous mechanical properties under tidal breathing induces a spatially unique interstitial flow and shear stress distribution in the interstitial space. This may in turn trigger pulmonary fibroblast differentiation and neoalveolation. In this study, we developed a theoretical basis for how cyclic motion of the primary septal walls with heterogeneous mechanical properties affects the interstitial flow and shear stress distribution. The velocity field of the interstitial flow was expressed by a Fourier (complex) series and its leading term was considered to induce the basic structure of stress distribution as long as the dominant length scale of heterogeneity is the size of collapsed alveoli. We conclude that the alteration of mechanical properties of the primary septa caused by pneumonectomy can develop a new interstitial flow field, which alters the shear stress distribution. This may trigger the differentiation of resident fibroblasts, which may in turn induce spatially unique neoalveolation in the remaining lung. Our example illustrates that the initial forming of new alveoli about half the size of the original ones.
authors.affiliation: Faculty of Mechanical Engineering, Technion-Israel Institute of Tecnology, Haifa 32000, Israel.
authors.forename: Shimon
authors.initials: S
authors.lastname: Haber
authors.affiliation: Faculty of Mechanical Engineering, Technion-Israel Institute of Tecnology, Haifa 32000, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Weisbord
authors.affiliation: Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
authors.affiliation: Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Mentzer
authors.affiliation: Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA, United States. Electronic address: atsuda@hsph.harvard.edu.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuda
mesh_terms: D056151:Airway Remodeling; D000465:Algorithms; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D045604:Extracellular Fluid / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D008168:Lung / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D011013:Pneumonectomy / Q000379:methods*; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D051381:Rats; D013314:Stress, Mechanical; D013997:Time Factors