The extracellular matrix is a critical determinant of cell structure and function, and understanding cell-matrix interactions is area of significant current interest. However, characterizing the relationship between the matrix and cells is intractable in vivo; tools are not available to adequate manipulate matrix properties in a living organism. Thus the approach to addressing this problem that has emerged is based on engineered microenvironments, where advanced fabrication technologies from physics and engineering are used to build well-defined environments. But even with the many technical advances in this area, a unifying conceptual framework in which to present findings is lacking. For example, how does one compare the response of cells on surfaces with certain types of protein patterns to those on surfaces with specific topographic features? Here we propose to advance the state of the art in using advanced nanometer scale patterning and fabrication technologies to study the relationship between topographic signals and biochemical signals in controlling cellular responses. We propose to use focused ion beam milling to produce fibers that are organized similar to natural extracellular matrix, and combine these with patterns of proteins to which cells are known to respond. These data will then be analyzed using a novel information theoretic framework, using a spatial information metric (the k-space information). By varying the topographic and biochemical signals independently, we will establish how information from these two classes of signals interacts to modulate structural and functional responses of cells.
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