Contact Information:
e-mail:
phone: (217) 244-0793
fax: (217) 333-5052
127 Roger Adams Lab
MC-712, Box C-3
600 S. Mathews Ave.
Urbana, IL 61801
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.
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).
E.J. Hukkanen, J.A. Wieland, A. Gewirth, D.E. Leckband and R.D. Braatz, "Multiple-bond kinetics from single-molecule pulling experiments: Evidence for multiple NCAM bonds," Biophys. J., 89, 3434-3445 (2005).
J.A. Wieland, A.A. Gewirth and D.E. Leckband, "Single molecule measurements of the impact of lipid phase behavior on anchor strengths," J. Phys. Chem. B, 109, 5985-5993 (2005).
R.C. Gunawan, E.R. Choban, J.E. Conour, J. Silvestre, L.B. Schook, H.R. Gaskins, D.E. Leckband and P.J.A. Kenis, "Regiospecific control of protein expression in cells cultured on two-component counter gradients of extracellular matrix proteins," Langmuir, 21, 3061-3068 (2005).
C.P. Johnson, G. Fragneto, O. Konovalov, V. Dubosclard, J.F. Legrand and D.E. Leckband, "Structural studies of the neural-cell-adhesion molecule by X-ray and neutron reflectivity," Biochemistry, 44, 546-554 (2005).
C.P. Johnson, I. Fujimoto, U. Rutishauser and D.E. Leckband, "Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion," J. Biol. Chem., 280, 137-145 (2005).
