The flow of liquid on mucosal surfaces is ubiquitous in human physiology. The failure of cilia and airflow induced liquid flow in the lungs (mucus clearance), as in Cystic Fibrosis, primary cilia dyskinesis, and environmentally damaged lungs, leads to severe health problems as the lung tissue will be destroyed by infections that cannot be cleared. Significant progress has been made in recent years in identifying the key genetic mutation responsible for Cystic Fibrosis, studying the hydrodynamics and biochemistry of airway mucus and beginning to develop effective treatments. In parallel, theory and simulation have begun to tackle issues such as the basis for force production in biological molecules, the rheology of biological fluids and hydrodynamics of viscous, complex flows. We stand at a critical time when an understanding of biological systems assembled into a unified simulation is essential for making breakthroughs in the science of microbiological hydrodynamics. The approach of this project is to develop sophisticated physics-based models of polymer dynamics and viscoelastic hydrodynamics in close coordination with experiments in human bronchial epithelial cell cultures. Through a combination of established and advanced techniques, the project will develop an integrated view of the biophysics of the mucus clearance system from the molecular scale seen by signaling molecules and viruses, up to the millimeter scales that control flow. By combining a team of researchers from Applied Mathematics, Chemistry, Physics and Astronomy, Biochemistry and Biophysics, and the Cystic Fibrosis Center, the long term goal is to develop an integrated computational model that will be able to predict and evaluate truly effective therapeutic strategies. The challenge in developing this comprehensive approach is to proceed through a series of research goals that accomplish short range impact. ? ? ?
| Quammen, Cory W; Taylor 2nd, Russell M; Krajcevski, Pavel et al. (2016) The Virtual Pediatric Airways Workbench. Stud Health Technol Inform 220:295-300 |
| Guilluy, Christophe; Osborne, Lukas D; Van Landeghem, Laurianne et al. (2014) Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus. Nat Cell Biol 16:376-81 |
| Hill, David B; Vasquez, Paula A; Mellnik, John et al. (2014) A biophysical basis for mucus solids concentration as a candidate biomarker for airways disease. PLoS One 9:e87681 |
| Levy, Rachel; Hill, David B; Forest, M Gregory et al. (2014) Pulmonary fluid flow challenges for experimental and mathematical modeling. Integr Comp Biol 54:985-1000 |
| Herschlag, Gregory; Garcia, Guilherme J M; Button, Brian et al. (2013) A mechanochemical model for auto-regulation of lung airway surface layer volume. J Theor Biol 325:42-51 |
| Mitran, Sorin (2013) Continuum-kinetic-microscopic model of lung clearance due to core-annular fluid entrainment. J Comput Phys 244:193-211 |
| Garcia, Guilherme J M; Boucher, Richard C; Elston, Timothy C (2013) Biophysical model of ion transport across human respiratory epithelia allows quantification of ion permeabilities. Biophys J 104:716-26 |
| Cribb, J A; Vasquez, P A; Moore, P et al. (2013) Nonlinear signatures of entangled polymer solutions in active microbead rheology. J Rheol (N Y N Y) 57:1247 |
| Stukalin, Evgeny B; Cai, Li-Heng; Kumar, N Arun et al. (2013) Self-Healing of Unentangled Polymer Networks with Reversible Bonds. Macromolecules 46: |
| Lindley, Brandon S; Forest, M Gregory; Smith, Breannan D et al. (2012) Spatial Stress and Strain Distributions of Viscoelastic Layers in Oscillatory Shear. Math Comput Simul 82:1249-1257 |
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