Living tissues are intricate ensembles of cells of different types embedded in complex and well defined structures of extracellular matrix (ECM). Cell orientation and migration within tissues can be guided both by the organization of ECM and gradients of extracellular chemical ligands. Cell migration is essential for such diverse processes as tissue repair and regeneration following injury, innate immune response, cancer metastasis and various developmental events. Unfortunately, our ability to analyze cell polarization and migration is severely limited by the lack of devices capable of precise definition of the cell micro-environment, both in terms of gradients of chemical cues and nano-scale level control of the cell substratum. In this application, we propose to develop and test a series of biomimetic micro-devices combining the advantages of precise definition of both nano-topographic features and micro-scale fluid flows leading to generation of complex sets of guidance cues. We hypothesize that the combined effects of the nano-topography and spatially distributed signaling ligands will be integrated into the cell polarity and migration decisions through regulated localization (and dimensions) of focal adhesions and redistribution of the occupancy of the receptor binding sites. We anticipate that the proposed work will result in both increased understanding of the fundamental aspects of establishment of cell polarity and guidance, and allow us to establish general principles for development of more precise and defined scaffolds for tissues engineering.
This research is aimed at understanding of how diverse cell functions are controlled by the nano-scale features of cell micro-environment. These features mimic the extracellular matrix found in the natural cell micro-environment, but can also be used to guide cell behavior in a desired manner. Therefore, the exploratory research proposed in this application will have important implications for advanced tissues engineering problems, of high potential relevance to public health.
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