title: Nonthermal ATP-dependent fluctuations contribute to the in vivo motion of chromosomal loci.
abstract: Chromosomal loci jiggle in place between segregation events in prokaryotic cells and during interphase in eukaryotic nuclei. This motion seems random and is often attributed to brownian motion. However, we show here that locus dynamics in live bacteria and yeast are sensitive to metabolic activity. When ATP synthesis is inhibited, the apparent diffusion coefficient decreases, whereas the subdiffusive scaling exponent remains constant. Furthermore, the magnitude of locus motion increases more steeply with temperature in untreated cells than in ATP-depleted cells. This "superthermal" response suggests that untreated cells have an additional source of molecular agitation, beyond thermal motion, that increases sharply with temperature. Such ATP-dependent fluctuations are likely mechanical, because the heat dissipated from metabolic processes is insufficient to account for the difference in locus motion between untreated and ATP-depleted cells. Our data indicate that ATP-dependent enzymatic activity, in addition to thermal fluctuations, contributes to the molecular agitation driving random (sub)diffusive motion in the living cell.
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Weber
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Spakowitz
authors.forename: Julie A
authors.initials: JA
authors.lastname: Theriot
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000465:Algorithms; D000963:Antimetabolites / Q000494:pharmacology; D002876:Chromosomes, Bacterial / Q000235:genetics* / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000235:genetics* / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004058:Diffusion; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D056426:Genetic Loci; D007700:Kinetics; D018715:Microscopy, Video; D009038:Motion; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019810:Sodium Azide / Q000494:pharmacology; D013696:Temperature; D059008:Time-Lapse Imaging; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D014475:Uncoupling Agents; D000255:Adenosine Triphosphate; D019810:Sodium Azide; D003847:Deoxyglucose; D019297:2,4-Dinitrophenol; D012293:Rifampin