[Show abstract][Hide abstract] ABSTRACT: How cells correct for stochasticity to coordinate the chromosome replication and cellular division cycle is poorly understood. We used time-lapse microscopy and fluorescently labelled SeqA to determine the timing of birth, initiation, termination, and division, as well as cell size throughout the cell cycle. We found that the time between birth and initiation (B-period) compensates for stochastic variability in birth size and growth rate. The time between termination and division (D-period) also compensates for size and growth variability, invalidating the notion that replication initiation is the principal trigger for cell division. In contrast, the time between initiation and termination (C-period) did not display such compensations. Interestingly, the C-period did show small but systematic decreases for cells that spontaneously grew faster, which suggests a coupling between metabolic fluctuations and replication. An auto-regressive theoretical framework was employed to compare different possible models of sub-period control.
[Show abstract][Hide abstract] ABSTRACT: Monitoring drift ice in the Arctic and Antarctic regions directly and by remote sensing is important for the study of climate, but a unified modeling framework is lacking. Hence, interpretation of the data, as well as the decision of what to measure, represent a challenge for different fields of science. To address this point, we analyzed, using statistical physics tools, satellite images of sea ice from four different locations in both the northern and southern hemispheres, and measured the size and the elongation of ice floes (floating pieces of ice). We find that (i) floe size follows a distribution that can be characterized with good approximation by a single length scale , which we discuss in the framework of stochastic fragmentation models, and (ii) the deviation of their shape from circularity is reproduced with remarkable precision by a geometric model of coalescence by freezing, based on random Voronoi tessellations, with a single free parameter expressing the shape disorder. Although the physical interpretations remain open, this advocates the parameters and as two independent indicators of the environment in the polar regions, which are easily accessible by remote sensing.
[Show abstract][Hide abstract] ABSTRACT: Science has a close but very complex relationship with technology (Latour, 1987). A simple phenomenon is that technology enables science by offering tools that provide new data or new kinds of data. In other cases, aspects or views of the empirical world may remain invisible until technology builds something that unveils them to the eyes of the scientific community. On a deeper level, building something may be a form of understanding. For example " complex networks " became prominent in all sectors of science in the late 1990s, at the time that the Internet became a common tool for research and for society at large. Before then, networks had been restricted for decades to smaller niches. This change was accompanied by a thrust of high throughput technologies to collect new data, but arguably many of the " network " data had already been available for many years. On a smaller scale, we want to suggest here that so called " smart polymers " (Galaev and Mattiasson, 1999; Kumar et al., 2007) could be a promising technological metaphor for the behavior of the bacterial nucleoid. We want to explore the analogy with the similarly " intelligent " behavior shaped into bacterial nucleoids by natural selection. But first, what is a smart polymer, and what does it do? In soft-matter physics, " smart, " or " stimulus-responsive, " polymers are technological polymer systems designed to effect a variety of responsive behaviors to external stimuli (Figure 1). Smart polymers respond to the environment they are in. They are engineered to be sensitive to a number of factors, such as solvency, temperature, humidity, pH, light, electrical and magnetic field, and to effect mechanical and chemical changes (Galaev and Mattiasson, 1999; Kumar et al., 2007; Chen and Chang, 2014). They can be realized as linear free chains in solution, or as surface-grafted brushes or gels. Usually, response to stimuli is achieved through the addition of specific reactive functional groups and side chains, or by the use of graft-and-block copolymers (two different polymers grafted together) with different chemical properties (e.g., hydrophyly). Effective smart polymers typically undergo large changes (e.g., conformational transitions) in response to just small changes in the environment (e.g., pH, temperature, ionic strength). One way to achieve this behavior is through the introduction of " pre-programmed " phase transitions. For example, the polymer undergoes a reversible collapse after an external stimulus is applied. The reversibility of this change may also be an important property, allowing to detect changes in both directions. To fix the ideas, a prevalent use for smart polymers is targeted drug delivery. A smart-polymer system may control the release of drugs until the desired target is reached, and it is sensed by either a chemical or physical response triggering the release of the drug by " uncaging " it. For example, a polymer site-specific conjugation to specific amino acid sites may induce a trigger in the concentration of a targeted protein (Hoffman et al., 2000). It is then evident that the bacterial nucleoid can be seen as a smart polymer (Dillon and Dorman, 2010; Muskhelishvili et al., 2010; Benza et al., 2012; Kleckner et al., 2014). Its degree of compaction and conformation are modulated by the cell's growth conditions and in response to specific external cues (Figure 1). It is a complex system made of a long DNA polymer associated with RNA and proteins that may play at least two roles: adapt the shape of the nucleoid through both specific and non-specific DNA binding, and change the physical properties of DNA through dynamic changes in DNA topology.
Full-text · Article · May 2015 · Frontiers in Microbiology
[Show abstract][Hide abstract] ABSTRACT: Using an approach inspired from Spin Glasses, we show that the multimode
disordered Dicke model is equivalent to a quantum Hopfield network. We propose
variational ground states for the system at zero temperature, which we
conjecture to be exact in the thermodynamic limit. These ground states contain
the information on the disordered qubit-photon couplings. These results lead to
two intriguing physical implications. First, once the qubit-photon couplings
can be engineered, it should be possible to build scalable pattern-storing
systems whose dynamics is governed by quantum laws. Second, we argue with an
example how such Dicke quantum simulators might be used as a solver of "hard"
combinatorial optimization problems.
Full-text · Article · Jan 2015 · Physical Review Letters
[Show abstract][Hide abstract] ABSTRACT: The mean size of exponentially dividing E. coli cells cultured at a fixed
temperature but different nutrient conditions is known to depend on the mean
growth rate only. The quantitative relation between these two variables is
typically explained in terms of cell cycle control. Here, we measure the
fluctuations around the quantitative laws relating cell size, doubling time and
individual growth rate. Our primary result is a predominance of cell
individuality: single cells do not follow the dependence observed for the means
between size and either growth rate or inverse doubling time. Additionally, the
population and the individual-cell growth rate differ in their dependencies on
division time, so that individuals with the same interdivision time but coming
from colonies in different growth conditions grow at different rates. An
interesting crossover in this cell individuality separates fast- and
slow-growth conditions, possibly relating these findings to genome replication
control. Secondly, extending previous findings focused on a single growth
condition, we also establish that the spread in both size and doubling times is
a linear function of the population means of these variables. By contrast, the
fluctuations in single-cell growth rates do not show the same universality.
Estimates of the division rate as a function of the measurable parameters imply
a link between the universal and individual trends followed by single cells and
a cell division control process which is sensitive to cell size as well as to
additional variables, but which encodes a single intrinsic length-scale.
[Show abstract][Hide abstract] ABSTRACT: Constraints can affect dramatically the behavior of diffusion processes.
Recently, we analyzed a natural and a technological system and reported that
they perform diffusion-like discrete steps displaying a peculiar constraint,
whereby the increments of the diffusing variable are subject to
configuration-dependent bounds. This work explores theoretically some of the
revealing landmarks of such phenomenology, termed "soft bound". At long times,
the system reaches a steady state irreversibly (i.e., violating detailed
balance), characterized by a skewed "shoulder" in the density distribution, and
by a net local probability flux, which has entropic origin. The largest point
in the support of the distribution follows a saturating dynamics, expressed by
the Gompertz law, in line with empirical observations. Finally, we propose a
generic allometric scaling for the origin of soft bounds. These findings shed
light on the impact on a system of such "scaling" constraint and on its
possible generating mechanisms.
[Show abstract][Hide abstract] ABSTRACT: We monitored the dynamics of cell dimensions and reporter GFP expression in individual E. coli cells growing in a microfluidic chemostat using time-lapse fluorescence microscopy. This combination of techniques allows us to study the dynamical responses of single bacterial cells to nutritional shift-down or shift-up for longer times and with more precision over the chemical environment than similar experiments performed on conventional agar pads. We observed two E. coli strains containing different promoter-reporter gene constructs and measured how both their cell dimensions and the GFP expression change after nutritional upshift and downshift. As expected, both strains have similar adaptation dynamics for cell size rearrangement. However, the strain with a ribosomal RNA promoter dependent reporter has a faster GFP production rate than the strain with a constitutive promoter reporter. As a result, the mean GFP concentration in the former strain changes rapidly with the nutritional shift, while that in the latter strain remains relatively stable. These findings characterize the present microfluidic chemostat as a versatile platform for measuring single-cell bacterial dynamics and physiological transitions.
[Show abstract][Hide abstract] ABSTRACT: Recent experimental results suggest that the E. coli chromosome feels a
self-attracting interaction of osmotic origin, and is condensed in foci by
bridging interactions. Motivated by these findings, we explore a generic
modeling framework combining solely these two ingredients, in order to
characterize their joint effects. Specifically, we study a simple polymer
physics computational model with weak ubiquitous short-ranged self attraction
and stronger sparse bridging interactions. Combining theoretical arguments and
simulations, we study the general phenomenology of polymer collapse induced by
these dual contributions, in the case of regularly-spaced bridging. Our results
distinguish a regime of classical Flory-like coil-globule collapse dictated by
the interplay of excluded volume and attractive energy and a switch-like
collapse where bridging interaction compete with entropy loss terms from the
looped arms of a star-like rosette. Additionally, we show that bridging can
induce stable compartmentalized domains. In these configurations, different
"cores" of bridging proteins are kept separated by star-like polymer loops in
an entropically favorable multi-domain configuration, with a mechanism that
parallels micellar polysoaps. Such compartmentalized domains are stable, and do
not need any intra-specific interactions driving their segregation. Domains can
be stable also in presence of uniform attraction, as long as the uniform
collapse is above its theta point.
[Show abstract][Hide abstract] ABSTRACT: The physical nature of the bacterial chromosome has important implications for its function. Using high-resolution dynamic tracking, we observe the existence of rare but ubiquitous 'rapid movements' of chromosomal loci exhibiting near-ballistic dynamics. This suggests that these movements are either driven by an active machinery or part of stress-relaxation mechanisms. Comparison with a null physical model for subdiffusive chromosomal dynamics shows that rapid movements are excursions from a basal subdiffusive dynamics, likely due to driven and/or stress-relaxation motion. Additionally, rapid movements are in some cases coupled with known transitions of chromosomal segregation. They do not co-occur strictly with replication, their frequency varies with growth condition and chromosomal coordinate, and they show a preference for longitudinal motion. These findings support an emerging picture of the bacterial chromosome as off-equilibrium active matter and help developing a correct physical model of its in vivo dynamic structure.
No preview · Article · May 2014 · Nature Communications
[Show abstract][Hide abstract] ABSTRACT: Prokaryotes vary their protein repertoire mainly through horizontal transfer and gene loss. To elucidate the links between
these processes and the cross-species gene-family statistics, we perform a large-scale data analysis of the cross-species
variability of gene-family abundance (the number of members of the family found on a given genome). We find that abundance
fluctuations are related to the rate of horizontal transfers. This is rationalized by a minimal theoretical model, which predicts
this link. The families that are not captured by the model show abundance profiles that are markedly peaked around a mean
value, possibly because of specific abundance selection. Based on these results, we define an abundance variability index
that captures a family's evolutionary behavior (and thus some of its relevant functional properties) purely based on its cross-species
abundance fluctuations. Analysis and model, combined, show a quantitative link between cross-species family abundance statistics
and horizontal transfer dynamics, which can be used to analyze genome ‘flux’. Groups of families with different values of
the abundance variability index correspond to genome sub-parts having different plasticity in terms of the level of horizontal
exchange allowed by natural selection.
Full-text · Article · May 2014 · Nucleic Acids Research
[Show abstract][Hide abstract] ABSTRACT: The coordination of cell growth and division is a long-standing problem in biology. Focusing on Escherichia coli in steady growth, we quantify cell division control using a stochastic model, by inferring the division rate as a function of the observable parameters from large empirical datasets of dividing cells. We find that (i) cells have mechanisms to control their size, (ii) size control is effected by changes in the doubling time, rather than in the single-cell elongation rate, (iii) the division rate increases steeply with cell size for small cells, and saturates for larger cells. Importantly, (iv) the current size is not the only variable controlling cell division, but the time spent in the cell cycle appears to play a role, and (v) common tests of cell size control may fail when such concerted control is in place. Our analysis illustrates the mechanisms of cell division control in E. coli. The phenomenological framework presented is sufficiently general to be widely applicable and opens the way for rigorous tests of molecular cell-cycle models.
Preview · Article · Feb 2014 · Proceedings of the National Academy of Sciences
[Show abstract][Hide abstract] ABSTRACT: Recent biophysical approaches have provided key insights into the enthalpic and entropic forces that compact the nucleoid in the cell. Our biophysical approach combines two complementary, non-invasive and label-free techniques: a precisely timed steerable optical trap and a high throughput microcapillary Coulter counter. We demonstrate the ability of the latter technique to probe the physical properties and size of many purified nucleoids, at the individual nucleoid level. The DNA-binding protein H-NS is central to the organization of the bacterial genome. Our results show that nucleoids purified from the Δhns strain in the stationary phase expand approximately five fold more than the form observed in WT bacteria. This compaction is consistent with the role played by H-NS in regulating the nucleoid structure and the significant organizational changes that occur as the cell adapts to the stationary phase. We also study the permeability to the flow of ions and find that in the experiment nucleoids behave as solid colloids.
No preview · Article · Dec 2013 · Integrative Biology
[Show abstract][Hide abstract] ABSTRACT: The development of a complex system depends on the self-coordinated action of a large number of agents, often determining unexpected global behavior. The case of software evolution has great practical importance: knowledge of what is to be considered atypical can guide developers in recognizing and reacting to abnormal behavior. Although the initial framework of a theory of software exists, the current theoretical achievements do not fully capture existing quantitative data or predict future trends. Here we show that two elementary laws describe the evolution of package sizes in a Linux-based operating system: first, relative changes in size follow a random walk with non-Gaussian jumps; second, each size change is bounded by a limit that is dependent on the starting size, an intriguing behavior that we call "soft bound." Our approach is based on data analysis and on a simple theoretical model, which is able to reproduce empirical details without relying on any adjustable parameter and generates definite predictions. The same analysis allows us to formulate and support the hypothesis that a similar mechanism is shaping the distribution of mammalian body sizes, via size-dependent constraints during cladogenesis. Whereas generally accepted approaches struggle to reproduce the large-mass shoulder displayed by the distribution of extant mammalian species, this is a natural consequence of the softly bounded nature of the process. Additionally, the hypothesis that this model is valid has the relevant implication that, contrary to a common assumption, mammalian masses are still evolving, albeit very slowly.
Preview · Article · Dec 2013 · Proceedings of the National Academy of Sciences
[Show abstract][Hide abstract] ABSTRACT: In bacteria, chromosomal architecture shows strong spatial and temporal organization, and regulates key cellular functions, such as transcription. Tracking the motion of chromosomal loci at short timescales provides information related to both the physical state of the nucleo-protein complex and its local environment, independent of large-scale motions related to genome segregation. Here we investigate the short-time (0.1-10 s) dynamics of fluorescently labelled chromosomal loci in Escherichia coli at different growth rates. At these timescales, we observe for the first time a dependence of the loci's apparent diffusion on both their subcellular localization and chromosomal coordinate, and we provide evidence that the properties of the chromosome are similar in the tested growth conditions. Our results indicate that either non-equilibrium fluctuations due to enzyme activity or the organization of the genome as a polymer-protein complex vary as a function of the distance from the origin of replication.
No preview · Article · Jun 2013 · Nature Communications
[Show abstract][Hide abstract] ABSTRACT: We examine the phenomenon of hydrodynamic-induced cooperativity for pairs of flagellated micro-organism swimmers, of which spermatozoa cells are an example. We consider semiflexible swimmers, where inextensible filaments are driven by an internal intrinsic force and torque-free mechanism (intrinsic swimmers). The velocity gain for swimming cooperatively, which depends on both the geometry and the driving, develops as a result of the near-field coupling of bending and hydrodynamic stresses. We identify the regimes where hydrodynamic cooperativity is advantageous and quantify the change in efficiency. When the filaments' axes are parallel, hydrodynamic interaction induces a directional instability that causes semiflexible swimmers that profit from swimming together to move apart from each other. Biologically, this implies that flagella need to select different synchronized collective states and to compensate for directional instabilities (e.g., by binding) in order to profit from swimming together. By analyzing the cooperative motion of pairs of externally actuated filaments, we assess the impact that stress distribution along the filaments has on their collective displacements.
Full-text · Article · Mar 2013 · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics
[Show abstract][Hide abstract] ABSTRACT: The H-NS chromosome-organizing protein in E. coli can stabilize genomic DNA loops, and form oligomeric structures connected to repression of gene expression. Motivated by the link between chromosome organization, protein binding and gene expression, we analyzed publicly available genomic data sets of various origins, from genome-wide protein binding profiles to evolutionary information, exploring the connections between chromosomal organization, gene-silencing, pseudo-gene localization and horizontal gene transfer. We report the existence of transcriptionally silent contiguous areas corresponding to large regions of H-NS protein binding along the genome, their position indicates a possible relationship with the known large-scale features of chromosome organization.
Full-text · Article · Mar 2013 · Molecular BioSystems
[Show abstract][Hide abstract] ABSTRACT: Open-source software is a complex system; its development depends on the
self-coordinated action of a large number of agents. This study follows the
size of the building blocks, called "packages", of the Ubuntu Linux operating
system over its entire history. The analysis reveals a multiplicative diffusion
process, constrained by size-dependent bounds, driving the dynamics of the
package-size distribution. A formalization of this into a quantitative model is
able to match the data without relying on any adjustable parameters, and
generates definite predictions. Finally, we formulate the hypothesis that a
similar non-stationary mechanism could be shaping the distribution of mammal