Cytoskeletal dynamics and mechanics, cellular mechanotransduction, physics of biopolymer networks, cell adhesion and migration
Ph.D., Harvard University, 2004
Jane Coffin Childs Memorial Fund Fellow, 2005
Burroughs Wellcome Career Award, 2006
NIH Director's Pioneer Award, 2007
Alfred P. Sloan Foundation Fellow, 2008
Packard Fellow, David and Lucile Packard Foundation, 2008
Early Excellence Award, American Asthma Foundation 2012
We are interested in the physical properties of biological cells. The varied mechanical behavior of cells is determined by a dynamic and composite polymer network of > 100 proteins called the cytoskeleton. We develop tools to study the dynamic structure and biophysical behavior of these macromolecular assemblies at sub-micron length scales to study how forces generated by individual proteins are transmitted to cellular length scales.
Cytoskeletal materials also provide quite a number of interesting problems in soft condensed matter physics. In contrast to traditional flexible polymers or rigid rods, cytoskeletal polymers are semi-flexible and the energy required to bend the filament on micron length scales is comparable to thermal energy. The competition between enthalpic and entropic effects in the dynamics and deformation of semi-flexible networks lead to extremely rich and varied mechanical response of both entangled solutions and chemically cross-linked networks. In the living cell, these networks are driven far from equilibrium by molecular motors and proteins that regulate filament cross-linking and assembly. By reconstituting these networks from purified proteins in vitro, we can better understand these physical behaviors.
Sabass B, Gardel ML, Waterman CM, Schwarz U. High Resolution Traction Force Microscopy Based on Experimental and Computational Advances. Biophysical Journal 94:207-220, 2008 (PMCID: PMC2134850).
Gardel ML, Sabass B, Ji L, Danuser G, Schwarz US, Waterman CM. Traction Stress in focal adhesions correlates biphasically with actin retrograde flow speed. Journal of Cell Biology 183:999-1005, 2008 (PMID: 2600750).
S.A. Rizvi, E.M. Neidt, J. Cui, Z. Feiger, M.L. Gardel, S.A. Kozmin and D.R. Kovar. Identification of a Small Molecule Inhibitor of Formin-Mediated Actin Assembly. Chemistry and Biology 16(11):1158-68, 2009 (PMID: 19942139)
Stricker J, Sabass B, Schwarz US, Gardel ML. Optimization of traction force microscopy for micron-sized focal adhesions. J. Physics: Condensed Matter 22:19104, 2010 (PMID: 20523913)
Aratyn-Schaus Y and Gardel ML. Transient frictional slip between integrin and the ECM in focal adhesions under myosin-II tension. Current Biology, 20(13):1145-53, 2010 (PMID: 20541412)
Borghi N, Lowndes M, Maruthamuthu V, Gardel ML and Nelson J. Regulation of Cell Motile Behavior by Crosstalk between cadherin- and integrin-mediated adhesions. Proc. Natl Acad Sci, 107(30):13324-9, 2010 (PMID:20566866)
Smith M, Blankman E, Luettjohann L, Gardel ML, Waterman CM, Beckerle MC. A Zyxin-Mediated Mechanism for Actin Stress Fiber Maintenance and Repair. Developmental Cell, 19(3): 365-76, 2010 PMID 20833360
Aratyn-Schaus Y, Oakes PW, Gardel ML. Dynamic and Structural Signatures of Lamellar Actomyosin Force Generation. Molecular Biology of the Cell. 22: 1330-1339, 2011 (PMID: 21307339)
Maruthamuthu V, Sabass B, Schwarz US, Gardel ML. Cell-ECM Traction Force Modulates Endogenous Tension at Cell-Cell Contacts. Proc Natl Acad Sci U S A. Mar 22; 108 12: 4708-13, 2011 (PMID: 21383129)
Stricker J, Aratyn-Schaus Y, Oakes PW, Gardel ML. Spatiotemporal Constraints on the Force-Dependent Growth of Focal Adhesions. Biophysical Journal, 2011 100(12): 2883-93 (PMID: 21689521)
Oakes PW, Beckham Y, Stricker J, Gardel ML. Tension is required but not sufficient for focal adhesion maturation without a stress fiber template. Journal of Cell Biology, 196(3) 2012 (PMID:22291038)
Falzone TT, Lenz M, Kovar DR, Gardel ML, Assembly kinetics determine the architecture of a-actinin crosslinked F-actin networks. Nat Commun. 2012;3:861.
Lenz M, Thoresen T, Gardel ML and Dinner AR Contractile units in disordered actomyosin bundles arise from F-actin buckling., Phys Rev Lett. 2012;108:238107
Schwarz US and Gardel ML, United we stand - integrating the actin cytoskeleton and cell-matrix adhesons in cellular mechanotransduction. J Cell Sci. 2012;125:1-10.
Stachowiak MR, McCall PM, Thoresen T, Balcioglu HE, Kasiewicz L, Gardel ML and O'Shaughnessy B Self-Organization of Myosin II in Reconstituted Actomyosin Bundles., Biophys J. 2012;103:1265-1274