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Charles S. Wright

Publications and source records attributed to Charles S. Wright.

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The transition from homeostasis to stochasticity induced catastrophe

What are the signatures of the onset of catastrophe? Here we present the rich system physics characterizing the transition from homeostasis to stochasticity driven breakdown in an experimentally motivated minimal model. Recent high-precision experiments on individual bacterial cells, growing and dividing repeatedly in a variety of environments, have revealed a previously unknown intergenerational scaling law which not only uniquely determines the stochastic map governing homeostasis, but also, as we show here, offers quantitative insights into the transition from the "conspiracy principle" regime (homeostasis) to the "catastrophe principle" regime and then to system breakdown. In fact, upon closer examination, the stochastic map turns out to be a one-dimensional Kesten process; these transitions occur as a single parameter, the strength of the multiplicative noise term, is continuously tuned. Emergence of asymptotically scale invariant distributions with quantifiable power law tails, outlier driven extremal behavior and reverse monotonicity of the conditional exceedance distribution characterize this transition to catastrophe. In turn, prevention of rapid increase in the extremal event-driven rate of failure, in the interest of system preservation, causes the catastrophe regime to be strategically unfavorable.

cond-mat.stat-mech

Emergent Simplicities in the Living Histories of Individual Cells

Organisms maintain the status quo, holding key physiological variables constant to within an acceptable tolerance, and yet adapt with precision and plasticity to dynamic changes in externalities. What organizational principles ensure such exquisite yet robust control of systems-level "state variables" in complex systems with an extraordinary number of moving parts and fluctuating variables? Here we focus on these issues in the specific context of intra- and intergenerational life histories of individual bacterial cells, whose biographies are precisely charted via high-precision dynamic experiments using the SChemostat technology. We highlight intra- and intergenerational scaling laws and other "emergent simplicities" revealed by these high-precision data. In turn, these facilitate a principled route to dimensional reduction of the problem, and serve as essential building blocks for phenomenological and mechanistic theory. Parameter-free data-theory matches for multiple organisms validate theory frameworks, and explicate the systems physics of stochastic homeostasis and adaptation.

cond-mat.stat-mech

Emergent Spatiotemporal Organization in Stochastic Intracellular Transport Dynamics

The interior of a living cell is an active, fluctuating, and crowded environment. Yet, it maintains a high level of coherent organization, which is readily apparent in the intracellular transport network. Membrane-bound compartments called endosomes play a key role in carrying cargo, in conjunction with myriad components including cargo adaptor proteins, membrane sculptors, motor proteins, and the cytoskeleton. These components coordinate to effectively navigate the crowded cell interior and transport cargo to specific intracellular locations, even though the underlying protein interactions and enzymatic reactions exhibit stochastic behavior. A major challenge is to measure, analyze, and understand how, despite the inherent stochasticity of the constituent processes, the collective outcomes show an emergent spatiotemporal order that is precise and robust. This review focuses on this intriguing dichotomy, providing insights into the known mechanisms of noise suppression and noise utilization in intracellular transport processes, and also identifies opportunities for future inquiry.

physics.bio-ph

Bridging the time scales of single-cell and population dynamics

How are granular details of stochastic growth and division of individual cells reflected in smooth deterministic growth of population numbers? We provide an integrated, multiscale perspective of microbial growth dynamics by formulating a data-validated theoretical framework that accounts for observables at both single-cell and population scales. We derive exact analytical complete time-dependent solutions to cell-age distributions and population growth rates as functionals of the underlying interdivision time distributions, for symmetric and asymmetric cell division. These results provide insights into the surprising implications of stochastic single-cell dynamics for population growth. Using our results for asymmetric division, we deduce the time to transition from the reproductively quiescent (swarmer) to replication-competent (stalked) stage of the {\em Caulobacter crescentus} lifecycle. Remarkably, population numbers can spontaneously oscillate with time. We elucidate the physics leading to these population oscillations. For {\em C. crescentus} cells, we show that a simple measurement of the population growth rate, for a given growth condition, is sufficient to characterize the condition-specific cellular unit of time, and thus yields the mean (single-cell) growth and division timescales, fluctuations in cell division times, the cell age distribution, and the quiescence timescale.

q-bio.QM

Intergenerational continuity of cell shape dynamics in Caulobacter crescentus

We investigate the intergenerational shape dynamics of single Caulobacter crescentus cells using a novel combination of imaging techniques and theoretical modeling. We determine the dynamics of cell pole-to-pole lengths, cross-sectional widths, and medial curvatures from high accuracy measurements of cell contours. Moreover, these shape parameters are determined for over 250 cells across approximately 10000 total generations, which affords high statistical precision. Our data and model show that constriction is initiated early in the cell cycle and that its dynamics are controlled by the time scale of exponential longitudinal growth. Based on our extensive and detailed growth and contour data, we develop a minimal mechanical model that quantitatively accounts for the cell shape dynamics and suggests that the asymmetric location of the division plane reflects the distinct mechanical properties of the stalked and swarmer poles. Furthermore, we find that the asymmetry in the division plane location is inherited from the previous generation. We interpret these results in terms of the current molecular understanding of shape, growth, and division of C. crescentus

q-bio.CB

Scaling laws governing stochastic growth and division of single bacterial cells

Uncovering the quantitative laws that govern the growth and division of single cells remains a major challenge. Using a unique combination of technologies that yields unprecedented statistical precision, we find that the sizes of individual Caulobacter crescentus cells increase exponentially in time. We also establish that they divide upon reaching a critical multiple ($\approx$1.8) of their initial sizes, rather than an absolute size. We show that when the temperature is varied, the growth and division timescales scale proportionally with each other over the physiological temperature range. Strikingly, the cell-size and division-time distributions can both be rescaled by their mean values such that the condition-specific distributions collapse to universal curves. We account for these observations with a minimal stochastic model that is based on an autocatalytic cycle. It predicts the scalings, as well as specific functional forms for the universal curves. Our experimental and theoretical analysis reveals a simple physical principle governing these complex biological processes: a single temperature-dependent scale of cellular time governs the stochastic dynamics of growth and division in balanced growth conditions.

physics.bio-ph