Research
Functional Biomaterials
At the interface between materials and biology
We develop materials for probing cell and protein interactions at interfaces. These strategies have been applied to research projects spanning fundamental discovery to translational biotechnology solutions.
Stimuli Responsive Textures and Coatings
Stimuli-responsive polymers offer a rich variety of properties useful for dynamic interactions with biological systems and critical to applications ranging from cell culture systems to medical devices to tissue engineering. These “smart” materials can respond to a stimulus such as temperature, pH, light or electrical or magnetic fields. We have formulated polymers of the thermally-responsive N-isopropylacrylamide, or NIPAAm, that can be patterned into textures and surface coatings that regulate cell adhesion strength and guide cell organization. We have found that surface confinement of particles or patterned shapes produces an interface with switchable adhesion or adsorption properties, which can induce rapid cell detachment on demand. The swelling and shape distortion of the pattern triggered by the volume phase transition imparts forces at the adhesive interface that can be tuned to disrupt adhesion faster than any metabolic process. This mechanical switch is under investigation for a variety of applications from cell culture supports to self-cleaning surfaces.
Cell Adhesion Strength
Cell adhesion to extracellular matrices plays a central role in mediating and regulating important cellular processes including, cell migration, signaling during morphogenesis, tissue homeostasis, and wound healing. Receptor mediated adhesion is a tightly regulated process that involves the complex interplay between biochemical and mechanical events at the cell adhesive interface. To elucidate the structure-function relationships between the adhesive components, we combine surface engineering approaches with a hydrodynamic shear assay and complementary biochemical techniques. Our work has established the spatiotemporal contributions of focal adhesion components to adhesion strength and identified a nonlinear dependence on cell spreading. We have investigate the regulation of cell adhesion strength by the size and position of focal adhesions by engineering the cell adhesive interface to direct FA assembly to the periphery of the cell spreading area to delineate the cell adhesive area from the cell spreading area. These mechanistic insights into the key biophysical regulators of cell adhesion further our understanding of mechanotransduction so that we can manipulate cell adhesive interfaces on biomaterials to direct cell functions.
Combinatorial Biomaterials for Mechanobiology
Combinatorial and high-throughput approaches to screening cell responses to material properties accelerate the speed of discovery and facilitate the identification of cell instructive cues or trends that may be missed by discrete sampling. Recent appreciation for the effects that mechanical properties of the local microenvironment have on the cell functions that regulate development, homeostasis, and disease underscore the need to understand the interplay between mechanical and chemical signals. We have developed fabrication methods for orthogonal gradients that independently vary the mechanical and chemical properties of extracellular matrices to investigate cellular responses such as endothelium organization, osteoblast proliferation, and dendritic cell activation. These studies demonstrate the potential of soft combinatorial biomaterials to identify significant trends or patterns in biological responses over large ranges of matrix properties.
Support
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