University of Connecticut |
Polymer Program SeminarA Library of Bioactive, Self-Assembling Proteins for Artificial Extracellullar Matrices Friday, March 4, 2005 11:00 am , IMS Room 20 We have utilized protein engineering and molecular biology methods to develop a library of de novo protein polymers with useful biomaterials properties. These proteins have been engineered to include molecular recognition elements that (1) direct their self-assembly into multi-component hydrogels with tailored microstructure and topology, and (2) interact with different types of cell surface receptors in order to guide their growth and development. The overall protein design is based on a modular, multi-block architecture that includes independent associating end domains and flexible biofunctional linker domains. The associating end blocks are amphiphilic helices that serve as smart crosslinking agents of the hydrogel, whereas the central linker domain is a water soluble, disordered sequence that encodes specific cell binding and signaling functions of extracellular matrix (ECM) constituents. Production of these materials through recombinant DNA methods gives unmatched control over their specific structural and biofunctional attributes. This talk presents studies of a group of proteins with associating end domains that are engineered to self-assemble specifically into trimeric bundles. This bundling leads to the formation of a regular network structure in the hydrogels, which enables the presentation of specific bioactive signals to target cells in a localized and regulated fashion. Through the use of microscopic and cell proliferation assays, we show that these multi-functional hydrogels are capable of inducing appropriate cellular responses. Examples are provided where one or more signals is presented to human cell lines cultured on hydrogel-coated surfaces or porous matrices. In doing so, we illustrate the utility of flexibility and modularity in a biomaterial as a means to induce desired cellular responses. We believe that such a combinatorial approach to biomaterials for artificial ECM applications, in which the end user can choose from a library of bioactive modules, mixing and matching as needed, will be a useful strategy for tissue engineering.
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