MICRO-FABRICATED CELL ENVIRONMENTS
Surface chemistry and microfabrication tools are used to modify surfaces with precisely tailored chemical and biochemical properties. These platforms enable us to determine how the micro-environment modulates cell functions at a level that is virtually impossible to achieve in vivo. We can precisely control the spatial distribution and concentration fields of biochemical factors seen by cells, and the local mechanical environment. We demonstrated how chemotactic and adhesive molecules control cell migration and signaling, for example. Ongoing research is determining how cells integrate these different signals to regulate cell functions. For example, we recently determined how different adhesion proteins cooperate to regulate tumor cell motility, and demonstrated how adhesive gradients direct cell migration. The information obtained from these studies has wide ranging applications in the clinic and in basic biological science.
POLYMER COATINGS AND SMART MATERIALS.
We have a long-standing interest in determining how interfacial properties of materials control biomacromolecule and cell functions, particularly in the context of composite materials that embed biological components. Examples include biomaterials, sensors, targeted drug carriers, and functionalized nanoparticles. We are particularly interested in "Smart" polymers that undergo dramatic changes in their interfacial properties in response to environmental stimuli (temperature, pH). Several clinical applications exploit this switching, and we are exploring how those interfacial changes impinge on function of immobilized proteins and nonspecific protein and cell adsorption.
Poly(N-isopropylacrylamide)(PNIPAM) is a thermally responsive "smart" polymer that binds cells and proteins above 32°C, but reversibly releases them at lower temperature. This material is used for targeted drug delivery, reversible cell or protein capture, cell sheet engineering, and biosensing. We are determining how this thermal transition depends on the molecular weight and density of the polymer chains. We are also identifying molecular level design parameters for thin coatings that reversibly release intact cell sheets for tissue engineering applications. Our work addressed applications in targeted drug delivery and tissue engineering.
INTERFACIAL FORCES AND SURFACE CHEMISTRY.
This work uses molecular force measurements to quantify molecular level relationships between surface chemistry and the interfacial forces that control biomaterial interactions with proteins and cells. These precision tools elucidated molecular bases of biomaterial surface properties, defined design rules for biosensor surfaces, and identified design criteria for stealthy drug carriers. Applications of this work include biosensors, neutral polymer coatings for drug carriers, muco-adhesive coatings for orally delivered drug carriers, and thermo-responsive smart polymer coatings for tissue engineering.
BIOMATERIAL EFFECTS ON PROTEIN FOLDING
The powerful capabilities of proteins have inspired their use at abiotic, material surfaces for diverse applications as biosensors, biologic pharmaceuticals, tissue engineering scaffolds, and drug targets. When proteins interact with materials, their structure and conformational dynamics, and hence function, can be altered compared to those in solution and in vivo. But determining how surface materials alter protein folding stability in situ is difficult with current, mostly noninterfacial techniques. We are developing Fast Relaxation Imaging (FReI) in collaboration with the Gruebele research group to understand the design rules of materials that enhance protein folding stability and function. FReI has been used previously in-cells, but currently has untapped potential to study biomaterials. By extending the FReI approach to studies of protein folding on hydrogels, polymer brushes, and gradient materials that enable methodological measurement of a “library” of diverse surface compositions on a single substrate and to see how design rules translate from microscale to nanoscale materials.
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