title: Cell responses only partially shape cell-to-cell variations in protein abundances in Escherichia coli chemotaxis.
abstract: Cell-to-cell variations in protein abundance in clonal cell populations are ubiquitous in living systems. Because protein composition determines responses in individual cells, it stands to reason that the variations themselves are subject to selective pressures. However, the functional role of these cell-to-cell differences is not well understood. One way to tackle questions regarding relationships between form and function is to perturb the form (e.g., change the protein abundances) and observe the resulting changes in some function. Here, we take on the form-function relationship from the inverse perspective, asking instead what specific constraints on cell-to-cell variations in protein abundance are imposed by a given functional phenotype. We develop a maximum entropy-based approach to posing questions of this type and illustrate the method by application to the well-characterized chemotactic response in Escherichia coli. We find that full determination of observed cell-to-cell variations in protein abundances is not inherent in chemotaxis itself but, in fact, appears to be jointly imposed by the chemotaxis program in conjunction with other factors (e.g., the protein synthesis machinery and/or additional nonchemotactic cell functions, such as cell metabolism). These results illustrate the power of maximum entropy as a tool for the investigation of relationships between biological form and function.
authors.affiliation: Battelle Center for Mathematical Medicine, The Research Institute at the Nationwide Children's Hospital, and Departments of Pediatrics, Physics, Statistics, and Biophysics Graduate Program, The Ohio State University, Columbus, OH 43205.
authors.forename: Sayak
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Seok
authors.forename: Veronica J
authors.initials: VJ
authors.lastname: Vieland
authors.forename: Jayajit
authors.initials: J
authors.lastname: Das
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D055592:Biophysical Phenomena; D002633:Chemotaxis / Q000502:physiology*; D019277:Entropy; D004926:Escherichia coli / Q000378:metabolism* / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D000072236:Methyl-Accepting Chemotaxis Proteins; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins
keywords: cell signaling; correlated protein expressions; maximum caliber; statistical physics