Welcome to the Leckband Group!

Our Multidisciplinary Team!

Our research focuses on biology at interfaces. Why study this? More than 85% of drug targets are cell surface receptors. Cells communicate with their environments through cell surface receptors. Biosensor and biomaterials designs exploit molecular recognition at interfaces. Yet interfacial environments differ radically from bulk solution where most biomacromolecules are studied. This raises several questions: What’s special about interfaces? How can we study the interfacial properties that affect biological function? How can we use this knowledge to understand biological function and solve biomedical problems. Our ongoing research is described below.

Zwitterionic polymer binds proteins in solution

Biomaterials. 

What makes a material ‘biocompatible’? We are identifying fundamental material properties that affect material performance in clinical and industrial applications. We focus on material surfaces where biology and materials first meet. A key challenge to prevent unwanted protein adsorption and denaturation at interfaces (biofouling). We use nano scale force probes and surface analytical tools to identify molecular scale material properties that preserve or shut down biological functions. An innovative new approach that we are developing with the Gruebele lab (chemistry) enables us to directly image protein stability in situ in hybrid bio-materials at sub micron spatial resolution and millisecond time resolution.

 

Neural network on N-cadherin modified graphene scaffold

Cell Adhesion and Molecular Biophysics.

Cells are fundamental building blocks of tissues, and adhesion proteins are the biochemical glue that control cell attachment to biomaterials and cell organization in multicellular tissues. We focus on cadherins, which are essential adhesion and signaling hubs at cell-cell junctions in all tissues. Our biophysical studies reveal  how these nanomachines bind cells together and transmit forces, to regulate signaling and tissue functions. We use atomistic simulations, live cell imaging, protein and cell engineering, and quantitative adhesion measurements. Current research is investigating how inside-out signaling regulates cadherin adhesion. We are also exploring how confinement at cell-cell contacts alters cadherin binding interactions and the assembly of dense, intercellular adhesions.

We discovered that complexes of cadherins and growth factor receptors comprise key force transduction switches at cell-cell adhesions. Together, these receptors regulate cell proliferation and force transduction. Current research is investigating the mechanism of complex formation and its regulation by force. One approach uses a novel fluorescence imaging approach to quantify binding between cadherins and growth factor receptors on the membranes of live cells. We are also investigating how mutations in these receptors and the mechanical environment of tumors control breast epithelial morphogenesis and malignant transformation in 3D organoid cultures.

Force transduction signaling disrupts the vascular endothelium

MechanoBiology.

Mechanical cues are widely recognized to play a major role in regulating cell and tissue functions. We identify how cells sense force and use this information to both understand biological processes and control cell and tissue functions. A major component of our research involves developing engineering and analytical tools for exploring the interplay between mechanics, cell signaling, and tissue functions. Our path-breaking discoveries revealed how adhesion proteins transduce mechanical cues between cells to regulate signaling, proliferation, and tissue physiology. We also uncovered force transduction cascades that integrate cadherins, integrins and growth factor receptors in a global mechano-sensitive signaling network in tissues. Research projects are uncovering how these mechanisms contribute to cardiovascular disease and tumor progression. In collaboration with the Kong lab (UIUC), we used our findings to engineer neural networks and control paracrine secretion by mesenchymal stem cells. Recent projects include collaborations with clinical researchers, cell biologists, and tissue engineers.

 

Be bold. Be innovative. Join the team!