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		Search Text: Home/< Back ToThe Science/Cell and Tissue Morphodynamics
  Cell and Tissue Morphodynamics
    The Laboratory of Cell and Tissue Morphodynamics, led by Dr. Clare Waterman, has made pioneering discoveries into the complex and dynamic mechanical interactions between organelle systems within cells that are required for directed movement.
    On This Page
    
          Clare Waterman
  Clare Waterman, Ph.D.
          NIH Distinguished Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              The process of directed cellular movement is of critical importance to human health, as is observed when immune cells seek out infected tissues or metastatic cancer cells invade new organs. Dr. Waterman has made pioneering discoveries into the complex and dynamic mechanical interactions between organelle systems within cells that are required for directed movement. Her laboratory established that the two classes of cytoskeletal polymers—microtubules and filamentous actin (f-actin)—exhibit both direct structural interactions and regulatory interactions mediated by Rho GTPases; she also developed specific technologies, including quantitative fluorescent speckle microscopy (qFSM) to systematically dissect the critical features of these interactions.

When cells move directionally through the extracellular matrix (ECM) of complex glycoproteins that make up their environment, they do so by protruding their surface membrane in the direction of migration, forming stable focal adhesions of the protrusion to the ECM, pulling against the adhesion to move the cell body forward, and dissolving the older adhesion sites at the back to retract the rear edge. When integrin receptors on the cell surface bind to glycoproteins in the ECM, this generates signals that regulate the speed and direction of migration. Dr. Waterman is now focused on integration of the actin dynamics in the cell with the integrin signals from the ECM that direct cellular motility, which places her firmly at the intersection of two scientific focus areas.

Integrin signaling has been intensely studied by biochemists who tease apart the key features of glycoproteins that sit, for example, on the surface of white blood cells. However, integrins function not simply to transduce signals across the cell membrane; Their operation is inseparable from the dynamical forces of movement that are generated in the actin cytoskeleton. Very little is known about the dynamics of integrins, their linkage to the cytoskeleton, and how that link is tuned according to different cellular states.

To address these questions, Dr. Waterman’s laboratory uses a variety of advanced techniques that allow them to study cytoskeletal and adhesion dynamics, and measure minute forces. For example, the use of traction force microscopy allows Dr. Waterman to measure the forces between the cell and the ECM while fluorescence speckle microscopy allows her to measure protein dynamics. By correlating the forces with protein dynamics under different molecular perturbations, Dr. Waterman can bridge the intellectual gap between molecular signaling and physical changes that are the final effectors of movement.

In a paper published in Nature in 2010, Dr. Waterman and her colleagues took advantage of three-dimensional super-resolution fluorescence microscopy to describe for the first time, at the ultrastructural level, the blueprint for how proteins in focal adhesions are organized. They can now use this blueprint to explore the relationships between molecular perturbations, physical relationships, and force capabilities. Dr. Waterman is also applying proteomic approaches to identify critical regulators of force adhesion dynamics.

Key to Dr. Waterman’s approach is a willingness to embrace interdisciplinarity to solve complex biological problems. Her laboratory includes cell biologists, physicists, mathematicians, engineers, and mouse geneticists, which she views as critical to achieving her research goals.
  Images






          Image of an Actin Paxillin
      
        Click the image to expand
    Actin Paxillin


        
            Actin cytoskeleton (red) and the focal adhesion protein, paxillin (green), in a migrating fibroblast.


                      Image of F-Tractin
      
        Click the image to expand
    F-Tractin


        
            Actin cytoskeleton in a metastatic melanoma cell undergoing bleb-based migration in non-adhesive confinement.


                      Image of Fibroblast red pxn-green actin blue cortactin
      
        Click the image to expand
    Fibroblast red pxn-green actin blue cortactin


        
            Actin cytoskeleton (green), the focal adhesion protein, paxillin (red), and the actin regulatory protein cortactin (blue) in a migrating fibroblast.


                      Image of Lamin Tissue
      
        Click the image to expand
    Lamin Tissue


        
            Lectins (pink), the nuclear envelope protein Lap2B (Green), and DNA (blue) in a melanoma tumor in mouse skin.
      Image of an Actin Paxillin


                      
Image of F-Tractin


                      
Image of Fibroblast red pxn-green actin blue cortactin


                      
Image of Lamin Tissue
Featured Publications
                Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration.
            Authors:Plotnikov SV, Pasapera AM, Sabass B, Waterman CM
                                                                                                                        
            Cell
      
                2012 Dec 21;151(7):1513-27
        Read Publication
                      Nanoscale architecture of integrin-based cell adhesions.
            Authors:Kanchanawong P, Shtengel G, Pasapera AM, Ramko EB, Davidson MW, Hess HF, Waterman CM
                                                                                                                        
            Nature
      
                2010 Nov 25;468(7323):580-4
        Read Publication
                      Mechanical integration of actin and adhesion dynamics in cell migration.
            Authors:Gardel ML, Schneider IC, Aratyn-Schaus Y, Waterman CM
                                                                                            
            Annu. Rev. Cell Dev. Biol.
      
                2010 Jan 01;26:315-33
        Read Publication
                      Differential transmission of actin motion within focal adhesions.
            Authors:Hu K, Ji L, Applegate KT, Danuser G, Waterman-Storer CM
                                                                                                                        
            Science
      
                2007 Jan 05;315(5808):111-5
        Read Publication
                      Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration.
            Authors:Gupton SL, Waterman-Storer CM
                                                                                                                        
            Cell
      
                2006 Jun 30;125(7):1361-74
        Read Publication
  Meet the Team

    Clare Waterman

            Clare Waterman, Ph.D.
                NIH Distinguished Investigator
                Clare Waterman graduated from the Mount Holyoke college with a B.A. in biochemistry in 1989, received an M.S. in exercise science in 1991 from the University of Massachusetts, and received her Ph.D. in cell biology from the University of Pennsylvania in 1995. Prior to joining the NHLBI, she spent 9 years as a professor in the Department of Cell Biology at the Scripps Research Institute in La Jolla, CA. Dr. Waterman is a NIH Distinguished Investigator and has received numerous awards and honors for her work, including election in 2018 to the National Academy of Sciences. Dr. Waterman has made fundamental advances in the understanding of role of the cytoskeleton in cell movement and morphogenesis and has authored or coauthored more than 135 papers. She currently serves on the editorial boards of Current Biology and Journal of Microscopy. Dr. Waterman is a member of the American Society for Cell Biology, Royal Microscopical Society, Biophysical Society, and is a Council Member of Gordon Research Conferences Organization.
    
          Contact the lab
    50 South DrBethesda, MD 20814United States
        Phone:
                    301-435-2949
                Fax:
  Pasapera Limon
    
            Ana Pasapera Limon, Ph.D.
        

    Staff Scientist

        pasaperaam@mail.nih.gov
            William Shin
    
            William Shin, B.S.
        

    Scientific Support Staff

        shinw2@mail.nih.gov
            Fischer
    
            Robert Fischer, Ph.D.
        

    Staff Scientist

        fischerr2@mail.nih.gov
            Michelle Baird
    
            Michelle  Baird
        

    Graduate Student

        michelle.baird@nih.gov
            Mehdi Hamouda
    
            Mehdi Hamouda
        

    Graduate Student

        mehdi.hamouda@nih.gov
            Ankita Jha
    
            Ankita Jha
        

    Postdoctoral Fellow

        ankita.jha@nih.gov
            Martina Lerche
    
            Martina Lerche
        

    Postdoctoral Fellow

        martina.lerche@nih.gov
            Zbigniew Baster
        

    Postdoctoral Fellow

        zbigniew.baster@nih.gov
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