The aim of this program is to study the physical determinants of lung parenchymal function. We view lung parenchyma as a structure in which gas transport, elasticity, and hysteresis arise from physical properties controlling the configuration, mechanical stability, and efficacy of gas exchanging surfaces and small airways serving them. Static equilibrium and dynamic stability of parenchymal structures and hence lung function, are based in the nature of bounding structures, the connective tissue matrix, the gas-liquid interface, and their mechanical interactions. In turn, thes are governed by physiological processes controlling the molecular composition and the cellular microenvironment. Derangements of these processes alter structure and composition, and hence lung function. The goal of this program is to investigate newly discovered biophysical mechanisms that form the basis of lung function at each of these levels, th connections between levels, and the changes that occur in biologically important departures from the normal state. Our approach is multidisciplinary, involving investigators knowledgeable in respiratory physiology, physics, engineering mechanics, and biology of chemical mediators, thoracic disease, cell biology, mathematics, and computer science. Collective, the projects of this program address the cascade of events that culminate in normal or abnormal architecture, mechanics and gas transport.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL033009-08
Application #
3098311
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1984-12-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Lange, Janina R; Metzner, Claus; Richter, Sebastian et al. (2017) Unbiased High-Precision Cell Mechanical Measurements with Microconstrictions. Biophys J 112:1472-1480
Zhang, Guangzhi; Chen, Xian; Ohgi, Junji et al. (2016) Biomechanical simulation of thorax deformation using finite element approach. Biomed Eng Online 15:18
Lange, Janina R; Steinwachs, Julian; Kolb, Thorsten et al. (2015) Microconstriction arrays for high-throughput quantitative measurements of cell mechanical properties. Biophys J 109:26-34
Lang, Nadine R; Skodzek, Kai; Hurst, Sebastian et al. (2015) Biphasic response of cell invasion to matrix stiffness in three-dimensional biopolymer networks. Acta Biomater 13:61-7
An, Steven S; Askovich, Peter S; Zarembinski, Thomas I et al. (2011) A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening. Respir Res 12:8
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An, Steven S; Kim, Jina; Ahn, Kwangmi et al. (2009) Cell stiffness, contractile stress and the role of extracellular matrix. Biochem Biophys Res Commun 382:697-703
Shore, Stephanie A; Williams, Erin S; Zhu, Ming (2008) No effect of metformin on the innate airway hyperresponsiveness and increased responses to ozone observed in obese mice. J Appl Physiol 105:1127-33
Leung, Lester Y; Tian, David; Brangwynne, Clifford P et al. (2007) A new microrheometric approach reveals individual and cooperative roles for TGF-beta1 and IL-1beta in fibroblast-mediated stiffening of collagen gels. FASEB J 21:2064-73
Lenormand, Guillaume; Bursac, Predrag; Butler, James P et al. (2007) Out-of-equilibrium dynamics in the cytoskeleton of the living cell. Phys Rev E Stat Nonlin Soft Matter Phys 76:041901

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