Information is critical for cellular life

Abstract

Functional Organization of CellsThe ability to receive, process and respond to information is critical for cellular life. This ability arises from the cell signaling network that processes information from external and internal sources. There are at least three sources of information: chemical signals, cell shape and mechanical forces. Integrating and processing information from all of these sources to coordinately control multiple cellular machines is essential for both homeostasis and regulated change in cell state. A key feature of signaling networks is the topology of regulatory motifs. Determining regulatory motif topology and the resultant information processing capability requires an integrated computational approach that blends graph theory-based analyses to identify and characterize regulatory motifs with differential equation-based models to determine functional capabilities of these motifs and how information processing changes with time and specific locations within the cell. Graph theory analyses indicate that large networks have a head-to-head topology that results in a depletion of long loops and such systems appear to be more dynamically stable. Interactions between motifs such as feedfoward loops and bifans indicate that multi-motif organization may be critical for biological processes. Differential equation models show that a set of three stacked and nested feedforward loops that is spatially specified is required for the β-adrenergic receptor triggering of the differentiated state in podocytes. These predictions have been experimentally verified. Thus the size of regulatory motifs and how the motifs are juxtaposed with respect to each other give rise to functional organization. There is partial overlap between the structural organization that arises from the presence and location of intracellular organelles and functional organization. Together the functional and structural organization of the cell determines how information is integrated, and how this integrated information is used to co-ordinate and regulate biological processes.