Our laboratory is interested in how mammalian cells touch, feel and work together to form multi-cellular tissues and organs. Cell-to-cell interactions are mediated by cell adhesion molecules and the cytoskeleton, and carefully regulated. Since abnormal cell adhesion is common in diseases like cancer, understanding of cell adhesion should lead to novel treatments. Using biophysical and cell biological approaches, we are trying to tease out the mechanisms involved in the regulation of cell adhesion. One approach is to analyze cell interactions in a physiologically relevant three-dimensional matrix using a live-cell confocal microscope system (see our movies on Youtube). In addition, we are analyzing the regulation of cell adhesion strength using microfabricated force sensor and atomic force microscopy. Currently, our focus is on how cancer cells interact with each other to regulate their migration through surrounding extracellular matrix and neighboring cells. Our unique experimental approaches provide new perspectives on how proteins assemble to generate physical and dynamic cell adhesions essential for morphogenesis and metastasis.
Mechano-transduction of cells
We are interested in how cells generate and respond to mechanical forces. Using multi-faceted approaches that include biochemistry, live-cell imaging, micro-fabrication, 3D matrix, traction force analysis, and atomic force microscopy, we are trying to tease out mechanisms by which cells sense and regulate forces. Examples of our approaches are shown in our youtube page.
Membrane fusion at adhesive contacts
We recently found that, when membrane protrusions of epithelial or endothelial cells fold and touch their own plasma membrane, these self-contacts are eliminated by membrane fusion. Since two adhering cells rarely fuse, our observation implies that cells have an ability to discriminate self from neighboring membranes despite the identical surface chemistry of both self and cell-cell junctions. We know that this self-recognition process, at least initially, depends on cadherins, and is possibly regulated by mechanical factors.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Biomedical Engineering
Specialties / Focus
- Cancer Biology
- Cell Biology
- Cell Division and the Cytoskeleton
- Cellular Responses to Toxins and Stress
- Developmental Biology
- Differentiation, Morphogenesis and Wound Healing
- Organelle and Membrane Biology
- BIM 102 Cellular Dynamics, Fall
- BIM 202 Cell and Molecular Biology for Engineers, Fall
- BIM 222 Cytoskeletal Mechanics, Fall
Honors and Awards
- Hellman Family New Faculty Award, 2008
- Beckman Young Investigator Award, 2009
- NIH EUREKA R01, 2010
- American Society for Cell Biology
- Biomedical Engineering Society
- 2001 PhD Chemical Engineering The Johns Hopkins University
- 1996 BS Chemical Engineering Rutgers University
- 2006 Postdoc Cell Biology Stanford University
Wu ZY, Chiu CL, Lo E, Lee YJ, Yamada S, Lo SH. (2019) Hyperactivity of Mek in TNS1 knockouts leads to potential treatments for cystic kidney diseases. 10(12):871. doi: 10.1038/s41419-019-2119-7.
Cheah JS, Jacobs KA, Heinrich V, Lo SH, Yamada S. (2019) Force-induced recruitment of cten along keratin network in epithelial cells. Proc Natl Acad Sci U S A. 116(40):19799-19801.
Cheah JS, Yamada S. (2017) A simple elution strategy for biotinylated proteins bound to streptavidin conjugated beads using excess biotin and heat. Biochem Biophys Res Commun. 493(4):1522-1527.
Susman MW, Karuna EP, Kunz RC, Gujral TS, Cantú AV, Choi SS, Jong BY, Okada K, Scales MK, Hum J, Hu LS, Kirschner MW, Nishinakamura R, Yamada S, Laird DJ, Jao LE, Gygi SP, Greenberg ME, Ho HH. (2017) Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates. eLife 6. pii: e26509.
Renner DJ, Ewald ML, Kim T, Yamada S. (2017) Biochemical analysis of force-sensitive responses using a large-scale cell stretch device. Cell adhesion & migration 11 (5-6):504-513.
Lee E, Ewald ML, Sedarous M, Kim T, Weyers BW, Truong RH, Yamada S. (2016) Deletion of the cytoplasmic domain of N-cadherin reduces, but does not eliminate, traction force-transmission. Biochemical and biophysical research communications 478(4):1640-6.
Lee JK, Hu JC, Yamada S, Athanasiou KA. (2016) Initiation of Chondrocyte Self-Assembly Requires an Intact Cytoskeletal Network. Tissue engineering. Part A 22(3-4):318-25.
Sumida GM, Yamada S. (2015) Rho GTPases and the downstream effectors actin-related protein 2/3 (Arp2/3) complex and myosin II induce membrane fusion at self-contacts. The Journal of biological chemistry 290(6):3238-47.
Ueda S, Blee AM, Macway KG, Renner DJ, Yamada S. (2015) Force dependent biotinylation of myosin IIA by α-catenin tagged with a promiscuous biotin ligase. PloS one 10(3):e0122886.
Sumida, G. M. and Yamada, S. Self-contact elimination by membrane fusion. Proc Natl Acad Sci U S A. 110:18958, 2013
Jorrisch, M., Shih, W., and Yamada, S. Myosin IIA deficient cells migrate efficiently despite reduced traction forces at cell periphery. Biol Open 2:368, 2013
Cui, Y. and Yamada, S. N-cadherin dependent collective cell invasion of prostate cancer cells is regulated by the N-terminus of alpha-catenin. PLoS One 8:e55069, 2013
Shih, W., Yamada, S. N-cadherin as a key regulator of collective cell migration in a 3D environment. Cell Adh Migr. 6:513, 2012
Zhang, H., Sirish, P., Yamada, S., Mahakian, L. M., Chiamvimonvat, N., Ferrara K. W. Assessing the fate of the payload of heart-homing liposomes. J Control Release. 163:10, 2012
Steele, A., Sumida, G., and Yamada, S. Tandem LIM sequences do not enhance force sensitive accumulation. Biochem Biophys Res Commun. 422:653, 2012
Yamada, S., Cheung, A., Nguyen, T-N., Shih, W. The force bearing linkage of cadherin junctions. Book Chapter in Comprehensive Biophysics. Elsevier Inc. 2012
Shih, W., Yamada, S. N-cadherin-mediated cell-cell adhesion promotes cell migration in a three-dimensional matrix. J Cell Sci, 125:3661, 2012
Li, L., Hartley, R., Reissc, B., Sun, Y., Pu, J., Hoang, T., Yamada, S., Jiangb, J., Zhao, M. E-cadherin plays an essential role in collective directional migration of large epithelial sheets. Cell Mol Life Sci. 69:2779, 2012
Shih, W., Yamada, S. Live-cell imaging of migrating cells expressing fluorescently-tagged proteins in a three-dimensional matrix. J. Vis. Exp. (58), e3589, DOI: 10.3791/3589, 2011
Sumida, G. M., Tomita, T., Shih, W., Yamada, S. Myosin II activity dependent and independent vinculin recruitment to the sites of E-cadherin mediated cell-cell adhesion. BMC Cell Biol. 12:48, 2011
Uemura, A., Nguyen, T-N., Steele A. N., Yamada, S. The LIM domain of zyxin is sufficient for force-induced accumulation during cell migration. Biophys J. 101:1069, 2011
Ounkomol C, Yamada S, Heinrich V. (2010) Single-cell adhesion tests against functionalized microspheres arrayed on AFM cantilevers confirm heterophilic E- and N-cadherin binding. Biophys J. 99(12):L100-2.
Nguyen TN, Uemura A, Shih W, Yamada S. (2010) Zyxin-mediated actin assembly is required for efficient wound closure. J Biol Chem. 285(46):35439-45.
Shih W, Yamada S. (2010) Myosin IIA dependent retrograde flow drives 3D cell migration. Biophys J. 98(8):L29-31.
Pokutta S, Drees F, Yamada S, Nelson WJ, Weis WI. (2008) Biochemical and structural analysis of alpha-catenin in cell-cell contacts. Biochem Soc Trans. 36(Pt 2):141-7
Yamada, S. and Nelson, W. J. Localized RhoA activation regulates actomyosin contraction and compaction of epithelial cell-cell adhesion (2007) J Cell Biol. 178:517-27
Yamada, S. and Nelson, W. J. Synapses: sites of cell recognition, adhesion, and functional specification. (2007) Annu Rev Biochem. 76:267-94
Reilein, A. Yamada, S. and Nelson, W. J. (2005) Self-organization of an acentrosomal microtubule network at the basal cortex of polarized epithelial cells J Cell Biol. 171:845
Drees, F. Pokutta, S. Yamada, S. Nelson, W. J. and Weis, W. I. (2005) Alpha-catenin is a molecular switch that binds E-cadherin/beta-catenin and regulates actin filament assembly. Cell 123:903
Yamada, S. Pokutta, S. Drees, F. Weis, W. I. and Nelson, W. J. (2005) Deconstructing the cadherin-catenin-actin complex. Cell 123:889
Nelson, W. J. Drees, F. and Yamada, S. (2005) Interaction of cadherin with the actin cytoskeleton. Novartis Found Symp. 269:159
Yamada, S. and Kuo, S. C. (2003) The inside story of Brownian motion: Revealing intracellular mechanics. Biophysics 43:180
Yamada, S. Wirtz, D. and Coulombe, P. A. (2003) The mechanical properties of simple epithelial keratins 8 and 18: discriminating between interfacial and bulk elasticities. J Struct Biol. 143:45-55.
Yamada, S. Wirtz, D. and Coulombe, P. A. (2002) Pairwise assembly determines the intrinsic potential for self-organization and mechanical properties of keratin filaments. Mol Biol Cell. 13:382-91.
Coulombe, P. A. Ma, L. Yamada, S. and Wawersik, M. (2001) Intermediate filaments at a glance. J Cell Sci. 114:4345-7
Bousquet, O. Ma, L. Yamada, S. Gu, C. Idei, T. Takahashi, K. Wirtz, D. and Coulombe, P. A. (2001) The nonhelical tail domain of keratin 14 promotes filament bundling and enhances the mechanical properties of keratin intermediate filaments in vitro. J Cell Biol. 155:747-54.
Ma, L. Yamada, S. Wirtz, D. and Coulombe, P. A. (2001) A 'hot-spot' mutation alters the mechanical properties of keratin filament networks. Nat Cell Biol. 3:503-6.
Coulombe, P. A. Bousquet, O. Ma, L. Yamada, S. and Wirtz, D. (2000) The 'ins' and 'outs' of intermediate filament organization. Trends Cell Biol. 10:420-8.
Yamada, S. Wirtz, D. and Kuo, S. C. (2000) Mechanics of living cells measured by laser tracking microrheology. Biophys J. 78:1736-47.