$268 Journal of Biomechanics 2006, Vol. 39 (Suppl 1) images generated from the model were similar to the real experimental images under normal and collapsed conditions. Conclusion: The proposed alveolar model gives an integrated explana- tion to several unsolved problems of respiratory pathophysiology; alveolar recruitment-derecruitment, mechanism of surfactant function, histologic find- ings of acute alveolar damage, and the origin of closing volume. 5431 Tu, 17:15-17:30 (P24) Micromechanics of the lung: from the parenchyma to the cytoskeleton D. Stamenovi6. Department of Biomedical Engineering, Boston University, Boston, MA, USA Lung parenchyma is a tensed stress-supported structure. The key distending stress, transpulmonary pressure, is transmitted by a tensed parenchymal lattice composed of the extracellular matrix (ECM), surface film and the contractile apparatus. This stress confers, in a nearly direct proportion, the parenchymal shear modulus and the associated forces of elastic interdependence that are critical in maintaining the shape of organ, region, vessel and alveolus. At each of these levels, this distending stress is essential for lung function, including stability of airspaces, distributions of ventilation and perfusion, fluid balance, and expiratory flow limitation. In the normal lung, the tensed ECM is the scaffold to which many pulmonary cells adhere. These cells use their contractile appa- ratus to probe their mechanical microenvironment in order to orient, spread, contract, remodel, differentiate and proliferate. Force transmission between cells and the ECM is bidirectional. Contractile stress, generated within the cytoskeletal lattice, is transmitted to the ECM via focal adhesions. In turn, focal adhesions transmit the distending stress of the ECM into the cytoskeleton. By utilizing similar mechanisms as the parenchyma, the cytoskeletal distending stress confers, in nearly direct proportion, shear modulus to the cell stabilizing thereby cell's shape. The distending stress of the cytoskeleton is a result of the interplay between the stress generated by contractile apparatus and the stress generated by distension of the ECM. At low to moderate levels of ECM distension, these two stresses work in concert, but at higher levels of ECM distension, contractile force generation may be hampered and thus cell stiffness reduced. Nevertheless, even if contractile apparatus is inhibited, the ECM distension can confer shear modulus to the cell. In summary, in the lung at each level - the ECM, surface film, the contractile apparatus, and the cytoskeleton - the distending stress emerges as a recurring and unifying agent. Its role is to confer stability to each of these levels, which is essential for normal function of the lung. 13.4. Pulmonary Cell Mechanics 6389 We, 08:15-08:45 (P28) Advances in pulmonary cell mechanics: Mechanical properties, structure and function D. Isabey. Biom~canique Ceflulaire et Respiratoire, Inserm UMR651 et Universit~ Paris XII Val-de-Mame, Facult~ de M6decine, Cr~teil, France Pulmonary adherent cells and extracellular matrix contribute to confer elastic properties, both at the micro scale, by establishing a relatively soft environment for tissue cells, and at the macroscale, by providing to lung tissue the ability to recover its shape notably after lung inflation. Normal tissue cells anchor, and stabilize their shape, through internal tension borne by the cytoskeleton struc- ture, or pull on their surroundings by applying forces generated by the acto- myosin cytoskeleton machinery. In all these processes, adhesion molecules such as integrins, cadherins, and a variety of other molecules, play a crucial role. There is an emerging recognition that tissue cells not only apply forces, but also sense biomechanical properties of their environment. However, quantitative studies on cell sensitivity to substrate mechanical properties remain scarce. Tissue cells are known to respond to changes in mechanical environment by reorganizing their cytoskeleton and likely modulate their own mechanical prop- erties but in an unknown manner. Lung diseases result in dramatic changes in cellular/tissues mechanical properties which could affect cell structural response and cell sensitivity to environment. We characterized mechanical sensitivity of alveolar epithelial cells and alveolar macrophages, two very different pulmonary cell types in terms of structure and function, to increasing stress applied through coated ferromagnetic beads and/or to increasing magnitudes of substrate stiffness. We found that, these two types of pulmonary cells, although presenting some similarities, exhibit important differences in terms of their response to applied stress/strain as well as sensitivity to substrate stiffness. Altogether, these results suggest cellular- function-dependent links between cytoskeleton remodelling, dynamic control of adhesion sites, and mechanotransduction processes. Oral Presentations 7732 We, 08:45-09:00 (P28) Central role of prestress in stress propagation in airway smooth muscle cells N. Wang. University of Illinois at Urbana-Champaign, IL, USA Current prevailing models of mechanotransduction focus on diffusion-based or translocation-based cascades originating from the cell surface to the cytoplasm and into the nucleus after initial stress activation of integrin receptors. We present evidence that induced strains were concentrated in the cytoplasm and inside the nucleus (the nucleolus) of the airway smooth muscle cells quite remote (>20 ~m) from the localized load of physiologic magnitudes (Hu et al, 2003, 2004, 2005), a finding that departs dramatically from conventional cell model predictions. These results suggest that direct mechanical activation of biochemical activities may occur deep in the cytoplasm and inside the nucleus, far away from cell surface receptors. Importantly, the distance and the efficiency of force propagation were dependent on the prestress in the cytoskeleton. We found that strains were not propagated to remote sites in plectin (a 500 kda cytoskeletal cross-linking protein)-deficient cells when compared with normal controls. Tractions in plectin-deficient cells were about 50% of those in control cells. These results are consistent with the model that the prestress in the actin bundles is central in mediating stress propagation along the cytoskeleton and into the nucleus (Wang and Suo, 2005). References Hu S., et al. (2003). Intracellular stress tomography reveals stress focusing and structural anisotropy in the cytoskeleton of living cells. Am. J. Physiol. Cell Physiol 285: C1082-1090. Hu S., et al. (2004). Mechanical anisotropy of adherent cells probed by a three dimensional magnetic twisting device. Am J Physiol Cell Physiol 287: Cl184- 1191. Hu S., et al. (2005). Prestress mediates force propagation into the nucleus. Biochem Biophys Res Commun 329: 423-428. Wang N., Suo Z. (2005). Long-distance propagation of forces in a cell. Biochem Biophys Res Commun 328:1133-1138. 4370 We, 09:00-09:15 (P28) Plasma membrane stress failure and repair in ventilator injured lungs R.D. Hubmayr. Mayo Clinic College of Medicine; Department of Physiology and Biomedical Engineering. Rochester, MN, USA The clinical and experimental literature has unequivocally established that mechanical ventilation with large tidal volumes is injurious to the lung. However, uncertainty about the micro-mechanics of injured lungs and the numerous degrees of freedom in ventilator settings leave many unanswered questions about the biophysical determinants of lung injury. I will focus my remarks on the experimental evidence for lung cells as injury targets and the relevance of these studies for human ventilator-associated lung injury. In vitro, the stress induced mechanical interactions between matrix and adherent cells are important for cellular remodeling as a means for preventing compromise of cell structure and ultimately cell injury or death. In vive these same principles apply. Large tidal volume mechanical ventilation results in physical breaks in alveolar epithelial and endothelial plasma membrane integrity and subsequent triggering of pro-inflammatory signaling cascades resulting in the cytokine milieu and pathologic and physiologic findings of ventilator-associated lung injury. Importantly though, alveolar cells possess cellular repair and remodeling mechanisms that in addition to protecting the stressed cell provide potential molecular targets for the prevention and treatment of ventilator-associated lung injury in the future. I will review the mechanisms by which externally deformed cells maintain sublytic plasma membrane tension, present experimental data on plasma membrane tether mechanics as a means of studying deformation induced membrane remodeling in type II cells and conclude with a discussion on the importance of environmental factors such as gas tension and osmotic pressure on membrane trafficking and cell repair in injured lungs. 6613 We, 09:15-09:30 (P28) Invited presentation (pulmonary cell mechanics): cell tractions and migration in 3D matrices B. Fabry. Biophysics group, University of Erlangen-Nuemberg, Erlangen, Germany Mechanical cell properties have been studied mainly in 2D cell culture systems. Cells cultured on flat, rigid substrates, however, behave differently from cells that are suspended in a 3D connective tissue matrix. For example, cells in 3D culture systems exhibit a more elongated morphology, less pronounced stress fiber formation, and they show marked differences in focal adhesion composition. To study the migration and invasion behavior of cells derived from lung tissue, including various epithelial lung tumor cell lines, we developed a 3D collagen gel invasion assay. In this assay, cells are plated onto the gels and are then allowed to invade into the gels. Invaded tumor cells commonly assume a spindle-like morphology and contract the gel predominantly along their primary axis. Contractile forces during cell invasion can be measured by extending