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Micromechanics of airway smooth muscle cells in culture Acute narrowing of the airway lumen in asthma is driven by myosin motors that exert their mechanical effects within a cytoskeletal scaffolding that is both deformable and in a continuous state of remodeling. The mechanical properties of that scaffolding are not well defined. This BRP grant is a multi-discliplinary design-directed bioengineering project that is intended to fill that gap of knowledge. We have developed a micro-nano scale mechanical technology to
measure the rheological properties of adherent living airway smooth muscle cells in culture, and the time-course of mechanical changes that occur in response to contractile stimuli or after genetic manipulation of cytoskeletal proteins. Ligand-coated ferromagnetic microbeads are bound to the cytoskeleton, and oscillatory
mechanical torques are then applied to the bead by a sinusoidally-varying external magnetic field. Resulting oscillatory bead motions deform the cell, and can be determined by measuring changes of the remanent magnetic field due to bead rotations or, alternatively, by direct observation of oscillatory bead displacements using light microscopy; these are complementary detection methods each with special advantages. This technology becomes, in effect, a micro-rheometry system that can probe – in cell culture conditions – contractile responses and underlying cellular rate processes over time scales as short as milliseconds to as long as hundreds of seconds, and with deformations as big as 500 nm and as small as 5 nm. Thus, it measures mechanical properties of cells using deformation times and deformation magnitudes that span the
physiological range. We are currently refining the technology and, as a proof of concept, using it to test the hypothesis that the contractile response of human airway smooth muscle cells in
culture is attenuated by overexpression of heat shock protein 27 (HSP27) dominant negative mutants. This hypothesis bears upon a question whose importance has been identified only recently, namely, the stability of the cytoskeleton of the airway smooth muscle cell and the role of CSK stability in airway narrowing in asthma. | Projektleitung: Prof. Dr. Ben Fabry
Stichwörter: Mikromechanik glatter Muskelzellen; Entwicklung von Verfahren zur Messung mechanischer Zellkräfte
Laufzeit: 1.9.2005 - 31.8.2010
Förderer: Harvard School of Public Health
Mitwirkende Institutionen: Dalhousie Universität (Kanada) Universität Barcelona (Spanien)
Kontakt: Fabry, Ben Telefon +49 (0) 9131 85-25610, Fax +49 (0) 9131 85-25601, E-Mail: bfabry@biomed.uni-erlangen.de
| Publikationen |
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Stamenovic, D. ; Suki, B. ; Fabry, Ben ; Wang, N. ; Fredberg, J. J.: Rheology of airway smooth muscle cells is associated with cytoskeletal contractile stress. In: J Appl Physiol 96 (2004), S. 1600-05 | Puig-de-Morales, M. ; Millet, E. ; Fabry, Ben ; Navajas, D. ; Wang, N. ; Butler, J. P. ; Fredberg, J. J.: Cytoskletal mechanics in adherent human airway smooth muscle cells: probe specificity and scaling of protein-protein dynamics. In: Am J Physiol Cell Physiol 287 (2004), S. C643-54 | Deng, L. ; Fairbank, N. J. ; Fabry, Ben ; Smith, P. G. ; Maksym, G. N.: Localized mechanical stress induces time-dependent actin cytoskeletal remodeling and stiffening in cultured airway smooth muscle cells. In: Am J Physiol Cell Physiol 287 (2004), S. C440-48 | Bursac, P. ; Lenormand, G. ; Fabry, Ben ; Oliver, M. ; Weitz, D. A. ; Viasnoff, V. ; Butler, J. P. ; Fredberg, J. J.: Cytoskeletal remodeling and slow dynamics in the living cell. In: Nature Materials (Letters) 4 (2005), S. 557-61 |
Institution: Lehrstuhl für Biophysik (Prof. Dr. Fabry)
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