title: Asymmetric Damage Segregation Constitutes an Emergent Population-Level Stress Response.
abstract: Asymmetric damage segregation (ADS) is a mechanism for increasing population fitness through non-random, asymmetric partitioning of damaged macromolecules at cell division. ADS has been reported across multiple organisms, though the measured effects on fitness of individuals are often small. Here, we introduce a cell-lineage-based framework that quantifies the population-wide effects of ADS and then verify our results experimentally in E. coli under heat and antibiotic stress. Using an experimentally validated mathematical model, we find that the beneficial effect of ADS increases with stress. In effect, low-damage subpopulations divide faster and amplify within the population acting like a positive feedback loop whose strength scales with stress. Analysis of protein aggregates shows that the degree of asymmetric inheritance is damage dependent in single cells. Together our results indicate that, despite small effects in single cell, ADS exerts a strong beneficial effect on the population level and arises from the redistribution of damage within a population, through both single-cell and population-level feedback.
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark; Niels Bohr International Academy, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark. Electronic address: svedel@nbi.ku.dk.
authors.forename: Søren
authors.initials: S
authors.lastname: Vedel
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark; Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Nunns
authors.affiliation: Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Andrej
authors.initials: A
authors.lastname: Košmrlj
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Semsey
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark. Electronic address: trusina@nbi.ku.dk.
authors.forename: Ala
authors.initials: A
authors.lastname: Trusina
mesh_terms: D060049:Asymmetric Cell Division; D002455:Cell Division; D020090:Chromosome Segregation; D004249:DNA Damage; D004926:Escherichia coli; D066329:Protein Aggregates; D013312:Stress, Physiological
chemical_list: D066329:Protein Aggregates