Chemistry at Illinois University of Illinois at Urbana-Champaign

Deborah E. Leckband

Reid T. Milner Professor of Chemical sciences
Professor of Chemistry (50%)
Professor of chemical and biomolecular Engineering

B.S., Humboldt State University, 1982
Ph.D., Cornell University, 1988
Postdoctorate, Massachusetts Institute of Technology and University of California, Santa Barbara, 1988-1992

Research

Research in the Biosurfaces Laboratory is at the interface between biology and surface science. Surfaces are ubiquitous in biology, and biological reactions at interfaces are central to a range of issues in medicine, biotechnology, and basic cell biology. For example, coatings on drug carriers increase blood circulation times and target blood borne delivery vehicles to specific tissues. Bio-recognition or enzymatic reactions at device surfaces are the basis of biosensors and microarrays. Nonspecific protein adsorption fouls contact lenses, implants, biosensors, and even ship hulls. In vivo, cell adhesion is essential for embryogenesis, wound healing, immunity, and a host of critical biological processes.

Our research is determining how the physical chemical properties of surfaces impacts fundamental biological functions and device/material performance in biological environments. We use state-of-the-art approaches to control surface chemistry, material properties, and the spatio-temporal distribution of cell stimuli. Biophysical measurements together with protein engineering and cell biology techniques determine how cells communicate with and respond to their environment. To address these issues, we are organized along two, closely coupled research themes.

The Biological Interfaces Group uses surface modification, micro-patterning, and materials synthesis to precisely manipulate cell microenvironments. These powerful tools control concentration profiles of soluble factors and adhesive cues. We also tune mechanical properties of scaffolds to mimic in vivo tissue environments, and thereby precisely control cell stimuli in ways that are difficult to achieve in vivo. Through collaborations with biologists both at UIUC and other institutions, we use these platforms to understand and manipulate cell behavior. Current projects (i) identify design rules for controlling material properties in aqueous/biological environments, (ii) determine how engineered adhesive and soluble cues direct stem cell differentiation, (ii) identify how the interplay between different adhesion receptors controls cell adhesion and migration in cancer metastasis, wound healing, and embryonic development.

Research achievements include identifying the molecular design criteria for drug delivery coatings and non-fouling contact lens materials. We similarly established design rules for "smart" coatings that change interfacial properties in response to a pH or temperature switch.

The Cell Adhesion Biophysics Group addresses fundamental mechanisms of cell adhesion (to other cells or biomaterials) and the transduction of mechano-chemical signals across cell membranes. We use a multi-scale approach to determine how the structures of protein nanomachines govern the organization and mechanical properties of cells in tissues. Simulations identify how protein bonds rupture under force (as in cell migration) and the key force-bearing amino acids in receptor-ligand bonds. Single molecule and surface force measurements test theoretical predictions and quantify the strengths and kinetics of biomolecular bonds. Adhesion measurements between single cells further translate the nanomechanical properties of protein linkages to the assembly of cell junctions in tissues. More recent work uses complementary mechanical and biochemical approaches to determine how adhesion proteins transduce signals across cell membranes to regulate cell function, cell migration, and the elasticity of normal and diseased tissues.

Highlights of the Adhesion Biophysics Group include determining how the presentation of carbohydrate binding sites in lectins impacts pathogen recognition in innate immunity. They also discovered novel mechanisms by which adhesion molecules zip up cell-cell junctions in tissues.

In summary, this research program uses novel tools to determine how cells communicate with their environment. The synergistic activities of the Biological Interfaces and Cell Adhesion Biophysics teams generate an exciting, dynamic, and highly interdisciplinary research environment. This is an ideal environment for individuals who seek novel, cross-disciplinary problems with direct implications for biotechnology and human health.

Publications

Maruthamuthu V, Schulten K, Leckband D. Elasticity and Rupture of a Multi-domain NCAM Complex. Biophys J. 2009, In press.

Shi Q, Chien YH, Leckband D. Biophysical properties of cadherin bonds do not predict cell sorting. J Biol Chem. 2008 Vol. 283, Issue 42, 28454-28463.

Leckband D. Beyond structure: mechanism and dynamics of intercellular adhesion. Biochem Soc Trans. 2008 Apr;36(Pt 2):213-20.

Chien YH, Jiang N, Li F, Zhang F, Zhu C, Leckband D. Two stage cadherin kinetics require multiple extracellular domains but not the cytoplasmic region. J Biol Chem. 2008 Jan 25;283(4):1848-56.

Zhu, X., Yan, C., Winnik, F.M., Leckband, D.E. End-Grafted Low Molecular Weight PNIPAM Does Not Collapse above the LCST, Langmuir. 2007 23(1):162-9

R. Dong, T.W. Jensen, R.G. Nuzzo, D.E. Leckband, "Variably elastic hydrogel patterned via capillary action in micro channels," Langmuir, 23, 1483-1488 (2007).

M.V. Bayas, A. Kearney, A. Avramovic, P.A. van der Merwe and D.E. Leckband, "Impact of salt bridges on the equilibrium binding and adhesion of human CD2 and CD58," J. Biol.l Chem., 282, 5589-5596 (2007).

A.K. Prakasam, V. Maruthamuthu and D.E. Leckband, "Similarities between heterophilic and homophilic cadherin adhesion," Proc. Nat. Acad. Sci. USA, 103, 15434-15439 (2006).

A. Prakasam, Y.H. Chien, V. Maruthamuthu and D.E. Leckband, "Calcium site mutations in cadherin: Impact on adhesion and evidence of cooperativity," Biochemistry, 45, 6930-6939 (2006).

X. Zhu, C. Yan, F.M. Winnik, D.E. Leckband, "End-grafted low molecular weight PNIPAM does not collapse above the LCST, Langmuir, (2007, in ASAP).

S.C. Wuang, K.G. Neoh, E.T. Kang, D.W. Pack and D.E. Leckband, "Heparinized magnetic nanoparticles: In-vitro assessment for biomedical applications," Adv. Functional Materials, 16, 1723-1730 (2006).

R.C. Gunawan, J. Silvestre, H.R. Gaskins, P.J.A. Kenis and D.E. Leckband, "Cell migration and polarity on microfabricated gradients of extracellular matrix proteins," Langmuir, 22, 4250-4258 (2006).

K.N. Plunkett, X. Zhu, J.S. Moore and D.E. Leckband, "PNIPAM chain collapse depends on the molecular weight and grafting density," Langmuir, 22, 4259-4266 (2006).

M. Bayas, A. Leung, E. Evans, D. Leckband, Lifetime measurements reveal kinetic differences between homophilic cadherin bonds, Biophys. J., 90, 1385-1395 (2006).

C. Yan, W. Matsuda, D.R. Pepperberg, S.C. Zimmerman and D.E. Leckband, "Synthesis and characterization of an electroactive surface that releases γ-aminobutyric acid (GABA)," J. Coll. Int. Sci., 296, 165-177 (2006).

Awards

Highlights

Chien, Y-H, Jiang, N., Li, F., Zhang, F., Zhu, C., Leckband, D. (2007) Two-stage cadherin kinetics require multiple extracellular domains but not the cytoplasmic region, J. Biol. Chem., 283:1848-5671.

These studies show how the nanomechanics and kinetics of single protein-protein bonds control the assembly of adhesive junctions between live cells.

Prakasam, A., Maruthamuthu, V., Leckband, D.E. (2006) Similarities between Heterophilic and Homophilic Cadherin Adhesion, Proc. Natnl Acad. Sci., 103, 15434-15439.

Molecular force measurements explored the molecular basis of binding specificity between adhesion proteins that is thought to underlie the segregation of cells into distinct tissues during embryogenesis.

Patents

Photo of Deborah E. Leckband