Deborah E. Leckband
- Molecular, Cellular and Tissue Engineering
- Postdoctorate, Massachusetts Institute of Technology and University of California, Santa Barbara, 1988-1992
- Ph.D., Cornell University, 1988
- B.S., Humboldt State University, 1982
- Professor of Chemical and Biiomolecular Engineering (50%) Professor of Chemistry (50%) Affiliate, Biochemistry Director, Bioengineering Graduate Program
For more information
- Molecular, Cellular and Tissue Engineering
- Bioengineering and Biophysics
A significant technological challenge facing the biotechnology and biomedical industries is the integration of biological entities, such as proteins, DNA, or cells, into manufactured devices and, conversely, the engineering of materials to promote defined cellular functions in devices and in engineered tissues. Efforts to shrink the dimensions of bioanalytical systems as well as to incorporate cells and grow tissues on engineered scaffolds are generating tremendous demand for knowledge of the influence of interfacial properties on biological function and methods for improving the biological compatibility of materials.
In our research, we use surface physical chemical approaches to understand the biology-material interface and to engineer that interface by designing material composition and architecture. A variety of modern surface analytical and biochemical tools allow us to address biology-surface interactions on several length scales. With direct force measurements we quantify the molecular forces that control, for example, cell adhesion on engineered substrates. Similar investigations of biological recognition at interfaces revealed how the forces between cells or biomolecules and material surfaces affect biological function. Complementary studies of biosensor performance and cell adhesion in turn demonstrate how these molecular interactions impact whole cells and even device performance. These findings are generating design rules for affinity technologies that range from biosensors to protein purification.
Biological adhesion is one area where biology and surface-science intersect. Cell adhesion, in particular, underlies a variety of processes, including cancer metastasis and wound healing. Investigations of adhesion proteins identified novel, molecular mechanisms of cell adhesion and detachment. Ours is the first to demonstrate that some adhesion proteins zip together soft cell-cell junctions by forming multiple, sequential bonds. These exciting results demonstrate the enormous potential of force measurements to determine how these complex cell surface proteins work. Our current efforts combine molecular biology and force measurements to elucidate biological adhesion mechanisms. This approach, together with cell culture studies, is further enabling the identification of protein fragments that can be used in scaffolds as biological cues to control cellular responses in artificial environments.
Other studies with biomedical polymers identified materials and solution conditions that promote or prevent bio-adhesion on a variety of materials. These latter studies are identifying molecular level design criteria for targeted drug delivery or non-fouling contact lens materials, for example.
We are using this knowledge to construct biologically active scaffolds for controlling the organization and growth of mammalian cells on engineered materials. In one project with Bruce Wheeler (Electrical Engineering), we are implementing these principles to control the growth of hippocampal neurons on patterned surfaces for potential applications in neural computing and in healing spinal chord injuries
Selected Articles in Journals
- Shashikanth, N, Newhall, J, Petrova, Y, Park, S, Ha, TJ, Gumbiner, BM, Leckband, DE (2015) Allosteric Regulation of E-Cadherin, J Biol Chem, 290: 21749-61.
- Li, J., Newhall, J., Ishiyama, N., Gottardi, C., Ikura, M., Leckband, D.E., and Tajkhorshid, E. (2015) Structural Determinants of the Mechanical Stability of Alpha Catenin, J Biol Chem 290:18890-903.
- Escobar, DJ, Desai, R, Ishiyama, N, Folmsbee, SS, Novak, MN, Flozak, AS, Daugherty RL, Mo, R, Nanavati, D, Sarpal, R, Leckband, D, Ikura, M, Tepass U, Gottardi CJ. (2015) α-catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism, J Cell Sci. 128: 1150-1165.
- Barry, A, Wang, N, Leckband, DE, (2015) Local VE-Cadherin Mechanotransduction Triggers Long-Ranged Remodeling of Endothelial Monolayers, J. Cell Sci,128: 134-51.
- Choi, S., Camp, S., Dan, A., Garcia, J.G.N., Dudek, S.M., Leckband, D. (2015) A Genetic Variant of Cortactin Linked to Acute Lung Injury Impairs Lamellipodia Dynamics and Endothelial Wound Healing, Am J Physiol: Cell Biology, in press.
- Vega L JC, Lee MK, Jeong JH, Smith CE, Lee KY, Chung HJ, Leckband DE, Kong H. (2014) Recapitulating cell-cell adhesion using N-cadherin biologically tethered to substrates, Biomacromolecules, 15: 2172-9.
- Leckband, D.E. and deRooij, J. (2014) Cadherin adhesion and mechanosensing, Ann Rev Cell Develop Biol, 30:291-315.
- Barry, A, Tabdili, H, Muhamed, I, Wu, J, Shashikanth, N, deRooij J, Gottardi, C, Yap, A, Wang, N, Leckband, D (2014) α-Catenin cytomechanics: role in cadherin-dependent adhesion and mechanotransduction, J. Cell. Sci. 127:1779-91.
- Kim, TJ, Zheng, S, Sun, J, Zho, Y, Cai, H, Muhammed, I, Leckband, DE, Wang, Y (2013) Visualizing force-dependent changes in a-catenin at cadherin adhesions, Curr Biol in press.
- Parreira P, Magalhães A, Reis CA, Borén T, Leckband D, Martins MC. (2013) Bioengineered surfaces promote specific protein-glycan mediated binding of the gastric pathogen Helicobacter pylori. Acta Biomaterialia, 9: 8885-8893.
- Ouyang, M, Lu, S, Kim, T, Chen, C-E, Seong, J., Leckband, DE, Wang, F, Reynolds, AB, Schwartz, MA, Wang, Y (2013) N-cadherin regulates spatially polarized signals through p120ctn and beta-catenin-dependent signaling pathways, Nature Communications, Article 1589.
- Choi, S, Choi, B-C, Xue, C, Leckband, D (2013) Protein adsorption mechanisms determine the efficiency of thermally controlled cell adhesion on poly(N-isopropyl acrylamide) brushes, Biomacromolecules,14: 92-100. Choi, B-C, Choi, S, Leckband, D (2013) Poly (N-isopropyl acrylamide) Brush Topography: relationship to film collapse and protein adsorption, Langmuir, 29: 5841-5850.
- Leckband, D. (2013) Sizing Up a Sticky Situation, Curr. Biol., R1008-R1011.
- Leckband, D. (2013) News and Views: Formin’ Cables Under Stress, Nat Cell Biol., 15: 345-346.
- Twiss F, Le Duc Q, Van Der Horst, S, Tabdili, H, Van Der Krogt, G, Wang, N, Rehmann, H, Huveneers S, Leckband DE, De Rooij J. (2012) Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation, Biol Open, 1:1128-40.
- Brouette, N, Xue, C, Haertkin, M, Moulin, M, Fragneto, G, Leckband, DE, Sferazza, M (2012) Antifouling properties of OEG monolayers and dense PNIPAM brushes probed by neutron reflectivity, Eur Phys J, 213: 343-353.
- Xue, C., Chan, B.C., Braun, P.V., Leckband, D.E. (2012) Protein Adsorption Modes Determine Reversible Cell Attachment on Poly(N-isopropyl acrylamide) Brushes, Adv Func Mat, 22: 2394–2401.
- Tabdili, H, Langer, M, Shi, Q, Poh, Y-C, Wang, N, Leckband, D (2012) Cadherin-dependent mechanotransduction depends on ligand identity but not affinity, J Cell Sci, 125:4362-71.
- Leckband, D.E., Sivasankar, S. (2012) Cadherin recognition and adhesion, Curr Op Cell Biol, 24: 620-627.
- Tabdili, H., Barry, A., Langer, M, Shi, Chien, Y.H., Q, Lee, KJ, Leckband, D (2011) Cadherin point mutations alter cell sorting and GTPase signaling, J Cell Sci, 125: 3299-309.
- Parreira, P., Magalhaes, A., Goncalves,I.C., Gomes, J., Vidal, R., Reis, C.A., Leckband, D.E., Martins, C.L. (2011) Effect of surface chemistry on bacterial adhesion, viability, and morphology, Biomed. Mat Res J, 99: 344-353.
- Langer, M.D., Guo, H., Shashikanth, N., Pierce, M., Leckband, D.E. (2011) N-Glycosylation Alters the Dynamics of N-Cadherin Junction Assembly, J Cell Sci, 125: 2478-2485.
- Andreasson-Ochsner, M., Romano, G., Hâkanson, M., Smith, M.L., Leckband, D.E., Textor, M., Reimhult, E. (2011) Single cell 3-D platform to study ligand mobility in cell–cell contact, Lab Chip, 11: 2876-83.
- Wuang, S.C., Neoh, K.G., Kang, E.T., Leckband, D.E., Pack, D.W. (2011) Acid-Sensitive Magnetic Nanoparticles as Potential Drug Depots. AIChE J, 15: 1638-1645.
- Xue, C., Yonet-Tanyeri, N., Brouette, N., Sferrazza, M., Braun, P.V., Leckband, D.E. (2011) Protein adsorption on poly (N-isopropyl acrylamide) brushes: dependence on grafting density and chain collapse, Langmuir, 27: 8810-8818.
- Leckband, D., leDuc, Q, Wang, N., deRooij, J (2011) Mechanosensing at Cadherin Adhesions, Curr Op Cell Biol 23: 523-530.
- Leckband, D (2011) Novel functions and binding mechanisms of carbohydrate-binding proteins identified from force measurements, Curr Protein & Peptide Sci, 12: 743-751.
- Niessen, C, Leckband, D, Yap, A. (2011) Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation, Physiol Rev, 91: 691-731.
- Leckband, DE, Menon, S, Rosenberg, K, Graham, S, Ward, E, Taylor, M, Drickamer, K (2010) Geometry of the extracellular domains of DC-SIGNR neck length variants analyzed by force-distance measurements, Biochemistry, 50: 6125-6132.
- Shi, Q, Maruthamuthu, V, Leckband, D (2010) Allosteric coupling between cadherin extracellular domains, Biophys J, 99: 95-104.
- Li, D, Zhou, J, Wang, L, Shin, ME, Su, P, Lei, P, Kuang, H, Guo, W, Yang, H, Tanaka, TS, Leckband, D, Reynolds, AB, Duan, E, Wang, F (2010) Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions, J. Cell Biol. 91: 631-644.
- Mann, C, Leckband, D (2010) Measuring Traction Forces in Long-Term Cell Cultures, Cell Mol Bioeng, 3: 40-49.
- le Duc Q, Shi Q, Blonk I, Sonnenberg A, Wang N, Leckband D, de Rooij J. (2010) Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner, J Cell Biol, 189: 1107-15.
- Leckband, D (2010) Design rules for biological adhesion: lessons from force measurements, Ann Rev Chem Biomol Eng, 1: 365-389.
- Parreira P, Reis CA, Magalhães A, Leckband D, Martins MCL. Immobilization of a Specific Receptor for H. pylori Using Model Surfaces. HELICOBACTER. 2009, 14(4): 410-411.
- Silvestre, J, Kenis, PJA, Leckband, D (2009) Cadherin and integrin regulation of epithelial cell migration, Langmuir, 25: 10092-9.
- J. Silvestre, P.J. Kenis, D.E. Leckband, "Cadherin and Integrin Regulation of Epithelial Cell Migration," Langmuir, 25, 10092-9 (2009). (PubMed abstract)
- Maruthamuthu, V, Schulten, KS, Leckband, D (2009) Elasticity and Rupture of the Multi-domain Hemophilic Complex of the Neural Cell Adhesion Molecule, Biophys. J, 96:3005-14.
- S. Menon, K. Rosenberg, S.A. Graham, E.M. Ward, M.E. Taylor, K. Drickamer, D.E. Leckband, "Surface force measurements demonstrate binding site geometry and flexibility in DC-SIGN," Proc. Natl. Acad. Sci,. USA, 106, 11524-9 (2009). (PubMed abstract)
- V. Maruthanmuthu, K. Schulten, D. Leckband, "Elasticity and rupture of a multi-domain neural cell adhesion molecule complex," Biophys J., 96, 3005-3014 (2009)
- Parreira, P., Reis, C., Magalhaes, A., Leckband, D., Martins, C. (2008) H-pylori adhesion to gold, hydrophilic, and hydrophobic self-assembled monolayers (SAMs), HELICOBACTER, 13: 415.
- Parreira P, Reis CA, MagalhÃ£es A, Leckband D, Martins MCL. Helicobacter pylori adhesion to gold, hydrophilic and hydrophobic self-assembled monolayers (SAMs). HELICOBACTER. 2008, 13(5):415-415
- Leckband, D (2008) From single molecules to living cells: nanomechanical measurements of cell adhesion, Cell Mol Bioeng, 1: 312-326.
- F. Chowdhury, S. Na, O. Collin, B. Tay, F. L, T. Tanaka, D.E. Leckband, N. Wang (2008) Is cell rheology governed by nonequilibrium-to-equilibrium transition of noncovalent bonds? Biophys. J., 95, 5719-5727.
- Q. Shi, Y.H. Chien, D. Leckband, "Biophysical properties of cadherin bonds do not predict cell sorting (2008) J. Biol. Chem., 283 28454-28463.
- D. Leckband, "Beyond structure: mechanism and dynamics of intercellular adhesion (2008) Biochem. Soc. Trans., 36, 213-220.
- S.C. Wuang, K.F. Neoh, E.T. Kang, D.W. Pack, D.E. Leckband (2008) HER-2-mediated endocytosis of magnetic nanospheres and the implications in cell targeting and particle magnetization, Biomaterials, 29, 2270-2279.
- Y.H. Chien, N. Jiang, F. Li, F. Zhang, C. Zhu, D. Leckband (20087) Two stage cadherin kinetics require multiple extracellular domains but not the cytoplasmic region, J. Biol. Chem., 283, 1848-1856.
- R. Dong, T.W. Jensen, R.G. Nuzzo, D.E. Leckband (2007) Variably elastic hydrogel patterned via capillary action in micro channels, Langmuir, 23, 1483-1488.
- M.V. Bayas, A. Kearney, A. Avramovic, P.A. van der Merwe and D.E. Leckband (2007) Impact of salt bridges on the equilibrium binding and adhesion of human CD2 and CD58," J. Biol Chem., 282, 5589-5596.
- V.I. Zarnitsyna, J. Huang, F. Zhang, Y.H. Chien, D. Leckband, C. Zhu (2007) "Memory in receptor-ligand-mediated cell adhesion," Proc. Natl. Acad. Sci. USA, 104: 18037-1842.
- Leckband, D, Prakasam, A (2006) Mechanism and dynamics of cadherin adhesion, Ann Rev Biomed Eng, 8: 259-287