Deborah Leckband

Professor, Chemical & Biomolecular Engineering

Physico-chemical mechanisms of cell communication with the environment

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.

Representative Publications

J. Silvestre, P.J. Kenis, D.E. Leckband, "Cadherin and Integrin Regulation of Epithelial Cell Migration," Langmuir, (in press, 2009). (PubMed abstract)

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)

F. Chowdhury, S. Na, O. Collin, B. Tay, F. L, T. Tanaka, D.E. Leckband, N. Wang, "Is cell rheology governed by nonequilibrium-to-equilibrium transition of noncovalent bonds?" Biophys. J., 95, 5719-5727 (2008).

Q. Shi, Y.H. Chien, D. Leckband, "Biophysical properties of cadherin bonds do not predict cell sorting," J. Biol. Chem., 283 28454-28463 (2008).

D. Leckband, "Beyond structure: mechanism and dynamics of intercellular adhesion," Biochem. Soc. Trans., 36, 213-220 (2008).

S.C. Wuang, K.F. Neoh, E.T. Kang, D.W. Pack, D.E. Leckband, "HER-2-mediated endocytosis of magnetic nanospheres and the implications in cell targeting and particle magnetization," Biomaterials, 29, 2270-2279 (2008)

Y.H. Chien, N. Jiang, F. Li, F. Zhang, C. Zhu, D. Leckband, "Two stage cadherin kinetics require multiple extracellular domains but not the cytoplasmic region," J. Biol. Chem., 283, 1848-1856 (2007).