A major challenge in cell and organism biology is to understand how living cell physiology emerges from the biophysical properties of individual macromolecules. The morphological and physical behaviors of cells required for cell adhesion, migration and division depend on the proper spatial and temporal regulation of a vast hierarchy of multi-protein machines, called the cytoskeleton. However, while we are gaining increasing amounts of knowledge of properties of individual cytoskeletal proteins, we have very little knowledge about the self-assembly and physical properties of multi-protein assemblies that form physical structures to transmit mechanical information up to cellular length scales. For example, we do not understand how forces generated by individual molecular motors are exploited by cytoskeletal assemblies to regulate morphogenesis and force generation at the cellular level. Current understanding of the physical behavior of the cellular cytoskeleton has been limited both by the lack of experimental techniques to probe the dynamic structure and physical properties of mesoscopic cytoskeletal assemblies in living cells. I propose to establish the experimental tools to study the biophysical properties of cytoskeletal matter in living cells by integrating approaches from condensed matter physics with molecular cell biology. This work will identify the underlying physics of emergent cytoskeletal assemblies and will provide predictive analytical models to link our understanding of the biophysics of molecules to cell behaviors. Finally, this work will impact the treatment of diseases that are a result of misregulation of the physical behaviors of cells, including cancer metastasis and cardiac diseases.
| Murrell, Michael; Thoresen, Todd; Gardel, Margaret (2014) Reconstitution of contractile actomyosin arrays. Methods Enzymol 540:265-82 |
| Oakes, Patrick W; Gardel, Margaret L (2014) Stressing the limits of focal adhesion mechanosensitivity. Curr Opin Cell Biol 30:68-73 |
| Gardel, Margaret Lise (2013) Materials science: Synthetic polymers with biological rigidity. Nature 493:618-9 |
| Birukova, Anna A; Tian, Xinyong; Cokic, Ivan et al. (2013) Endothelial barrier disruption and recovery is controlled by substrate stiffness. Microvasc Res 87:50-7 |
| Caswell, Thomas A; Zhang, Zexin; Gardel, Margaret L et al. (2013) Observation and characterization of the vestige of the jamming transition in a thermal three-dimensional system. Phys Rev E Stat Nonlin Soft Matter Phys 87:012303 |
| Lenz, Martin; Thoresen, Todd; Gardel, Margaret L et al. (2012) Contractile units in disordered actomyosin bundles arise from F-actin buckling. Phys Rev Lett 108:238107 |
| Lenz, Martin; Gardel, Margaret L; Dinner, Aaron R (2012) Requirements for contractility in disordered cytoskeletal bundles. New J Phys 14: |
| Norstrom, Melanie; Gardel, Margaret L (2011) Shear thickening of F-actin networks crosslinked with non-muscle myosin IIB. Soft Matter 2011:3228-3233 |
| Maruthamuthu, Venkat; Sabass, Benedikt; Schwarz, Ulrich S et al. (2011) Cell-ECM traction force modulates endogenous tension at cell-cell contacts. Proc Natl Acad Sci U S A 108:4708-13 |
| Thoresen, Todd; Lenz, Martin; Gardel, Margaret L (2011) Reconstitution of contractile actomyosin bundles. Biophys J 100:2698-705 |
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