Physical control of mammalian cell behavior
Exciting new strategies have recently emerged that engineer cell function by physical rather than chemical means. For example, hydrodynamic shear stress increases the speed of endothelial cell migration. Stem cell differentiation can be directed purely by varying the mechanical properties of the substrate. Controlling the degree of cell spreading alone can switch cells between growth, apoptosis and differentiation. In these experiments, the goal is to manipulate cell function by varying physical properties of the extracellular environment. This is critically important for the engineering of tissues, such as creating a blood vessel, owing to the ease and reliability of manipulating physical variables in vivo and in vitro. To ensure the success of these emerging strategies, it is vitally important to develop a sound fundamental understanding of how physical cues modulate gene expression. To do this, we are focusing on the effects of physical cues on a key process that controls gene expression: nuclear pore transport. We are also developing novel bioMEMs devices to control cell migration, directing neural stem cell differentiation with mechanical cues, and engineering the cell-material interface by controlling the nano-scale properties of the substrate.
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Fluorescence image of a single capillary endothelial cell spread and adherent on a glass substrate. The cell adheres to the substrate at discrete nano-scale protein complexes called focal adhesions (green). Tensile forces in contractile actin stress fibers (red) are transmitted to the substrate at focal adhesions, allowing cells to spread. The actin microfilament-focal adhesion coupling is central to cellular sensing of substrate properties, including substrate stiffness, nano-scale roughness and adhesive ligand presentation. Scale bar, 10 microns. |
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Lele TP and Ingber DE, Focal adhesions: self-assembling nanoscale mechano-chemical machines that control cell function.In: Nair L, Laurencin C, Halberstadt C, Gonsalves K, eds., Biomedical Nanostructures, John Wiley & Sons In Press.
Kumar S, Maxwell IZ, Heisterkamp A, Polte TR, Lele TP, Salanga M, Mazur E, Ingber DE, “Viscoelastic retraction of single living stress fibers and its impact on cell shape, cytoskeletal organization and extracellular matrix mechanics”, Biophysical Journal, 90: 3762-73 (2006).
Lele TP and Kumar SK, “Brushes, cables and ratchets: Recent insights into multiscale assembly and mechanics of cellular structural networks”, Cell Biochemistry and Biophysics, 47: 348-360 (2007).