Ariel Amir

Cell Size Regulation in Bacteria

Various rod-shaped bacteria such as the canonical gram negative Escherichia coli or the well-studied gram positive Bacillus subtilis divide symmetrically after they approximately double their volume. Their size at division is not constant, but is typically distributed over a narrow range. Here, we propose an analytically tractable model for cell size control, and calculate the cell size and inter-division time distributions. We suggest ways of extracting the model parameters from experimental data. Existing data for E. coli supports partial size control, and a particular explanation: a cell attempts to add a constant volume from the time of initiation of DNA replication to the next initiation event. This hypothesis explains how bacteria control their tight size distributions and accounts for the experimentally observed correlations between parents and daughters as well as the exponential dependence of size on growth rate.

Bending forces plastically deform growing bacterial cell walls.

Significance Regulation of cell wall growth is a process of fundamental importance in cell biology. In this paper, to our knowledge, we demonstrate for the first time that mechanical stress directly influences cell wall synthesis of bacteria. In a series of simple experiments, we elastically and plastically deform cell walls as they grow by applying anisotropic mechanical stresses to bacteria. Using a theory of dislocation-mediated growth, we explain how growth and form of the cell walls are quantitatively related to one another in bacteria. Cell walls define a cell’s shape in bacteria. The walls are rigid to resist large internal pressures, but remarkably plastic to adapt to a wide range of external forces and geometric constraints. Currently, it is unknown how bacteria maintain their shape. In this paper, we develop experimental and theoretical approaches and show that mechanical stresses regulate bacterial cell wall growth. By applying a precisely controllable hydrodynamic force to growing rod-shaped Escherichia coli and Bacillus subtilis cells, we demonstrate that the cells can exhibit two fundamentally different modes of deformation. The cells behave like elastic rods when subjected to transient forces, but deform plastically when significant cell wall synthesis occurs while the force is applied. The deformed cells always recover their shape. The experimental results are in quantitative agreement with the predictions of the theory of dislocation-mediated growth. In particular, we find that a single dimensionless parameter, which depends on a combination of independently measured physical properties of the cell, can describe the cell’s responses under various experimental conditions. These findings provide insight into how living cells robustly maintain their shape under varying physical environments.

Interrogating the Escherichia coli cell cycle by cell dimension perturbations

Significance How bacteria regulate cell division to achieve cell size homeostasis, with concomitant coordination of DNA replication, is a fundamental question. Currently, there exist several competing models for cell cycle regulation in Escherichia coli. We performed experiments where we systematically perturbed cell dimensions and found that average cell volume scales exponentially with the product of the growth rate and the time from initiation of DNA replication to the corresponding cell division. Our data support a model in which cells initiate replication on average at a constant volume per origin and divide a constant time thereafter. Bacteria tightly regulate and coordinate the various events in their cell cycles to duplicate themselves accurately and to control their cell sizes. Growth of Escherichia coli, in particular, follows a relation known as Schaechter’s growth law. This law says that the average cell volume scales exponentially with growth rate, with a scaling exponent equal to the time from initiation of a round of DNA replication to the cell division at which the corresponding sister chromosomes segregate. Here, we sought to test the robustness of the growth law to systematic perturbations in cell dimensions achieved by varying the expression levels of mreB and ftsZ. We found that decreasing the mreB level resulted in increased cell width, with little change in cell length, whereas decreasing the ftsZ level resulted in increased cell length. Furthermore, the time from replication termination to cell division increased with the perturbed dimension in both cases. Moreover, the growth law remained valid over a range of growth conditions and dimension perturbations. The growth law can be quantitatively interpreted as a consequence of a tight coupling of cell division to replication initiation. Thus, its robustness to perturbations in cell dimensions strongly supports models in which the timing of replication initiation governs that of cell division, and cell volume is the key phenomenological variable governing the timing of replication initiation. These conclusions are discussed in the context of our recently proposed “adder-per-origin” model, in which cells add a constant volume per origin between initiations and divide a constant time after initiation.

Simultaneous regulation of cell size and chromosome replication in bacteria

Bacteria are able to maintain a narrow distribution of cell sizes by regulating the timing of cell divisions. In rich nutrient conditions, cells divide much faster than their chromosomes replicate. This implies that cells maintain multiple rounds of chromosome replication per cell division by regulating the timing of chromosome replications. Here, we show that both cell size and chromosome replication may be simultaneously regulated by the long-standing initiator accumulation strategy. The strategy proposes that initiators are produced in proportion to the volume increase and is accumulated at each origin of replication, and chromosome replication is initiated when a critical amount per origin has accumulated. We show that this model maps to the incremental model of size control, which was previously shown to reproduce experimentally observed correlations between various events in the cell cycle and explains the exponential dependence of cell size on the growth rate of the cell. Furthermore, we show that this model also leads to the efficient regulation of the timing of initiation and the number of origins consistent with existing experimental results.

On relaxations and aging of various glasses

Slow relaxation occurs in many physical and biological systems. “Creep” is an example from everyday life. When stretching a rubber band, for example, the recovery to its equilibrium length is not, as one might think, exponential: The relaxation is slow, in many cases logarithmic, and can still be observed after many hours. The form of the relaxation also depends on the duration of the stretching, the “waiting time.” This ubiquitous phenomenon is called aging, and is abundant both in natural and technological applications. Here, we suggest a general mechanism for slow relaxations and aging, which predicts logarithmic relaxations, and a particular aging dependence on the waiting time. We demonstrate the generality of the approach by comparing our predictions to experimental data on a diverse range of physical phenomena, from conductance in granular metals to disordered insulators and dirty semiconductors, to the low temperature dielectric properties of glasses.

Dislocation-mediated growth of bacterial cell walls

Recent experiments have illuminated a remarkable growth mechanism of rod-shaped bacteria: proteins associated with cell wall extension move at constant velocity in circles oriented approximately along the cell circumference [Garner EC, et al., (2011) Science 333:222–225], [Domínguez-Escobar J, et al. (2011) Science 333:225–228], [van Teeffelen S, et al. (2011) PNAS 108:15822–15827]. We view these as dislocations in the partially ordered peptidoglycan structure, activated by glycan strand extension machinery, and study theoretically the dynamics of these interacting defects on the surface of a cylinder. Generation and motion of these interacting defects lead to surprising effects arising from the cylindrical geometry, with important implications for growth. We also discuss how long range elastic interactions and turgor pressure affect the dynamics of the fraction of actively moving dislocations in the bacterial cell wall.

Localization, anomalous diffusion, and slow relaxations: a random distance matrix approach.

We study the spectral properties of a class of random matrices where the matrix elements depend exponentially on the distance between uniformly and randomly distributed points. This model arises naturally in various physical contexts, such as the diffusion of particles, slow relaxations in glasses, and scalar phonon localization. Using a combination of a renormalization group procedure and a direct moment calculation, we find the eigenvalue distribution density (i.e., the spectrum), for low densities, and the localization properties of the eigenmodes, for arbitrary dimension. Finally, we discuss the physical implications of the results.

Classical diffusion of a quantum particle in a noisy environment.

We study the spreading of a quantum-mechanical wave packet in a tight-binding model with a noisy potential and analyze the emergence of classical diffusion from the quantum dynamics due to decoherence. We consider a finite correlation time of the noisy environment and treat the system by utilizing the separation of fast (dephasing) and slow (diffusion) processes. We show that classical diffusive behavior emerges at long times and we calculate analytically the dependence of the classical diffusion coefficient on the noise magnitude and correlation time. This method provides a general solution to this problem for arbitrary conditions of the noisy environment. The calculation can be done in any dimension, but we demonstrate it in one dimension for clarity of representation. The results are relevant to a large variety of physical systems, from electronic transport in solid-state physics to light transmission in optical devices, diffusion of excitons, and quantum computation.

Mean-field model for electron-glass dynamics

We study a microscopic mean-field model for the dynamics of the electron glass near a local equilibrium state. Phonon-induced tunneling processes are responsible for generating transitions between localized electronic sites, which eventually lead to the thermalization of the system. We find that the decay of an excited state to a locally stable state is far from being exponential in time and does not have a characteristic time scale. Working in a mean-field approximation, we write rate equations for the average occupation numbers

Electron Glass Dynamics

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