arXiv subjects

David J. Schwab

Publications and source records attributed to David J. Schwab.

46 records · Page 3Linked to original sources

arXiv2014

From Intracellular Signaling to Population Oscillations: Bridging Scales in Collective Behavior

Collective behavior in cellular populations is coordinated by biochemical signaling networks within individual cells. Connecting the dynamics of these intracellular networks to the population phenomena they control poses a considerable challenge because of network complexity and our limited knowledge of kinetic parameters. However, from physical systems we know that behavioral changes in the individual constituents of a collectively-behaving system occur in a limited number of well-defined classes, and these can be described using simple models. Here we apply such an approach to the emergence of collective oscillations in cellular populations of the social amoeba Dictyostelium discoideum. Through direct tests of our model with quantitative in vivo measurements of single-cell and population signaling dynamics, we show how a simple model can effectively describe a complex molecular signaling network and its effects at multiple size and temporal scales. The model predicts novel noise-driven single-cell and population-level signaling phenomena that we then experimentally observe. Our results suggest that like physical systems, collective behavior in biology may be universal and described using simple mathematical models.

physics.bio-ph↗

arXiv2014

Zipf's law and criticality in multivariate data without fine-tuning

The joint probability distribution of many degrees of freedom in biological systems, such as firing patterns in neural networks or antibody sequence composition in zebrafish, often follow Zipf's law, where a power law is observed on a rank-frequency plot. This behavior has recently been shown to imply that these systems reside near to a unique critical point where the extensive parts of the entropy and energy are exactly equal. Here we show analytically, and via numerical simulations, that Zipf-like probability distributions arise naturally if there is an unobserved variable (or variables) that affects the system, e. g. for neural networks an input stimulus that causes individual neurons in the network to fire at time-varying rates. In statistics and machine learning, these models are called latent-variable or mixture models. Our model shows that no fine-tuning is required, i.e. Zipf's law arises generically without tuning parameters to a point, and gives insight into the ubiquity of Zipf's law in a wide range of systems.

q-bio.NC↗

arXiv2012

The Energetic Costs of Cellular Computation

Cells often perform computations in response to environmental cues. A simple example is the classic problem, first considered by Berg and Purcell, of determining the concentration of a chemical ligand in the surrounding media. On general theoretical grounds (Landuer's Principle), it is expected that such computations require cells to consume energy. Here, we explicitly calculate the energetic costs of computing ligand concentration for a simple two-component cellular network that implements a noisy version of the Berg-Purcell strategy. We show that learning about external concentrations necessitates the breaking of detailed balance and consumption of energy, with greater learning requiring more energy. Our calculations suggest that the energetic costs of cellular computation may be an important constraint on networks designed to function in resource poor environments such as the spore germination networks of bacteria.

q-bio.MN↗

arXiv2011

Kuramoto model with coupling through an external medium

Synchronization of coupled oscillators is often described using the Kuramoto model. Here we study a generalization of the Kuramoto model where oscillators communicate with each other through an external medium. This generalized model exhibits interesting new phenomena such as bistability between synchronization and incoherence and a qualitatively new form of synchronization where the external medium exhibits small-amplitude oscillations. We conclude by discussing the relationship of the model to other variations of the Kuramoto model including the Kuramoto model with a bimodal frequency distribution and the Millennium Bridge problem.

nlin.CD↗

arXiv2010

Dynamical quorum-sensing and synchronization of nonlinear oscillators coupled through an external medium

Many biological and physical systems exhibit population-density dependent transitions to synchronized oscillations in a process often termed "dynamical quorum sensing". Synchronization frequently arises through chemical communication via signaling molecules distributed through an external media. We study a simple theoretical model for dynamical quorum sensing: a heterogenous population of limit-cycle oscillators diffusively coupled through a common media. We show that this model exhibits a rich phase diagram with four qualitatively distinct mechanisms fueling population-dependent transitions to global oscillations, including a new type of transition we term "dynamic death". We derive a single pair of analytic equations that allows us to calculate all phase boundaries as a function of population density and show that the model reproduces many of the qualitative features of recent experiments of BZ catalytic particles as well as synthetically engineered bacteria.

q-bio.CB↗

arXiv2009

Statistical Mechanics of Integral Membrane Protein Assembly

During the synthesis of integral membrane proteins (IMPs), the hydrophobic amino acids of the polypeptide sequence are partitioned mostly into the membrane interior and hydrophilic amino acids mostly into the aqueous exterior. We analyze the minimum free energy state of polypeptide sequences partitioned into alpha-helical transmembrane (TM) segments and the role of thermal fluctuations using a many-body statistical mechanics model. Results suggest that IMP TM segment partitioning shares important features with general theories of protein folding. For random polypeptide sequences, the minimum free energy state at room temperature is characterized by fluctuations in the number of TM segments with very long relaxation times. Simple assembly scenarios do not produce a unique number of TM segments and jamming phenomena interfere with segment placement. For sequences corresponding to IMPs, the minimum free energy structure with the wildtype number of segments is free of number fluctuations due to an anomalous gap in the energy spectrum, and simple assembly scenarios produce this structure. There is a threshold number of random point mutations beyond which the size of this gap is reduced so that the wildtype groundstate is destabilized and number fluctuations reappear.

cond-mat.soft↗

arXiv2009

Glassy states in fermionic systems with strong disorder and interactions

We study the competition between interactions and disorder in two dimensions. Whereas a noninteracting system is always Anderson localized by disorder in two dimensions, a pure system can develop a Mott gap for sufficiently strong interactions. Within a simple model, with short-ranged repulsive interactions, we show that, even in the limit of strong interaction, the Mott gap is completely washed out by disorder for an infinite system for dimensions $D\le 2$. The probability of a nonzero gap falls onto a universal curve, leading to a glassy state for which we provide a scaling function for the frequency dependent susceptibility.

cond-mat.str-el↗

arXiv2008

Rhythmogenic neuronal networks, pacemakers, and k-cores

Neuronal networks are controlled by a combination of the dynamics of individual neurons and the connectivity of the network that links them together. We study a minimal model of the preBotzinger complex, a small neuronal network that controls the breathing rhythm of mammals through periodic firing bursts. We show that the properties of a such a randomly connected network of identical excitatory neurons are fundamentally different from those of uniformly connected neuronal networks as described by mean-field theory. We show that (i) the connectivity properties of the networks determines the location of emergent pacemakers that trigger the firing bursts and (ii) that the collective desensitization that terminates the firing bursts is determined again by the network connectivity, through k-core clusters of neurons.

q-bio.NC↗

arXiv2008

How many species have mass M?

Within large taxonomic assemblages, the number of species with adult body mass M is characterized by a broad but asymmetric distribution, with the largest mass being orders of magnitude larger than the typical mass. This canonical shape can be explained by cladogenetic diffusion that is bounded below by a hard limit on viable species mass and above by extinction risks that increase weakly with mass. Here we introduce and analytically solve a simplified cladogenetic diffusion model. When appropriately parameterized, the diffusion-reaction equation predicts mass distributions that are in good agreement with data on 4002 terrestrial mammal from the late Quaternary and 8617 extant bird species. Under this model, we show that a specific tradeoff between the strength of within-lineage drift toward larger masses (Cope's rule) and the increased risk of extinction from increased mass is necessary to produce realistic mass distributions for both taxa. We then make several predictions about the evolution of avian species masses.

q-bio.PE↗

arXiv2007

Nucleosome Switching

We present a statistical-mechanical analysis of the positioning of nucleosomes along one of the chromosomes of yeast DNA as a function of the strength of the binding potential and of the chemical potential of the nucleosomes. We find a significant density of two-level nucleosome switching regions where, as a function of the chemical potential, the nucleosome distribution undergoes a "micro" first-order transition. The location of these nucleosome switches shows a strong correlation with the location of transcription-factor binding sites.

cond-mat.soft↗