arXiv subjects

Ned S. Wingreen

Publications and source records attributed to Ned S. Wingreen.

At least 55 records · Page 3Linked to original sources

arXiv2009

Accuracy of direct gradient sensing by cell-surface receptors

Chemotactic cells of eukaryotic organisms are able to accurately sense shallow chemical concentration gradients using cell-surface receptors. This sensing ability is remarkable as cells must be able to spatially resolve small fractional differences in the numbers of particles randomly arriving at cell-surface receptors by diffusion. An additional challenge and source of uncertainty is that particles, once bound and released, may rebind the same or a different receptor, which adds to noise without providing any new information about the environment. We recently derived the fundamental physical limits of gradient sensing using a simple spherical-cell model, but not including explicit particle-receptor kinetics. Here, we use a method based on the fluctuation-dissipation theorem (FDT) to calculate the accuracy of gradient sensing by realistic receptors. We derive analytical results for two receptors, as well as two coaxial rings of receptors, e.g. one at each cell pole. For realistic receptors, we find that particle rebinding lowers the accuracy of gradient sensing, in line with our previous results.

q-bio.CB↗

arXiv2009

Accuracy of direct gradient sensing by single cells

Many types of cells are able to accurately sense shallow gradients of chemicals across their diameters, allowing the cells to move towards or away from chemical sources. This chemotactic ability relies on the remarkable capacity of cells to infer gradients from particles randomly arriving at cell-surface receptors by diffusion. Whereas the physical limits of concentration sensing by cells have been explored, there is no theory for the physical limits of gradient sensing. Here, we derive such a theory, using as models a perfectly absorbing sphere and a perfectly monitoring sphere, which, respectively, infer gradients from the absorbed surface particle density or the positions of freely diffusing particles inside a spherical volume. We find that the perfectly absorbing sphere is superior to the perfectly monitoring sphere, both for concentration and gradient sensing, since previously observed particles are never remeasured. The superiority of the absorbing sphere helps explain the presence at the surfaces of cells of signal degrading enzymes, such as PDE for cAMP in Dictyostelium discoideum (Dicty) and BAR1 for mating factor alpha in Saccharomyces cerevisiae (budding yeast). Quantitatively, our theory compares favorably to recent measurements of Dicty moving up a cAMP gradient, suggesting these cells operate near the physical limits of gradient detection.

q-bio.CB↗

arXiv2009

Information processing and signal integration in bacterial quorum sensing

Bacteria communicate using secreted chemical signaling molecules called autoinducers in a process known as quorum sensing. The quorum-sensing network of the marine bacterium {\it Vibrio harveyi} employs three autoinducers, each known to encode distinct ecological information. Yet how cells integrate and interpret the information contained within the three autoinducer signals remains a mystery. Here, we develop a new framework for analyzing signal integration based on Information Theory and use it to analyze quorum sensing in {\it V. harveyi}. We quantify how much the cells can learn about individual autoinducers and explain the experimentally observed input-output relation of the {\it V. harveyi} quorum-sensing circuit. Our results suggest that the need to limit interference between input signals places strong constraints on the architecture of bacterial signal-integration networks, and that bacteria likely have evolved active strategies for minimizing this interference. Here we analyze two such strategies: manipulation of autoinducer production and feedback on receptor number ratios.

q-bio.MN↗

arXiv2009

Steps in the bacterial flagellar motor

The bacterial flagellar motor is a highly efficient rotary machine used by many bacteria to propel themselves. It has recently been shown that at low speeds its rotation proceeds in steps [Sowa et al. (2005) Nature 437, 916--919]. Here we propose a simple physical model that accounts for this stepping behavior as a random walk in a tilted corrugated potential that combines torque and contact forces. We argue that the absolute angular position of the rotor is crucial for understanding step properties, and show this hypothesis to be consistent with the available data, in particular the observation that backward steps are smaller on average than forward steps. Our model also predicts a sublinear torque-speed relationship at low torque, and a peak in rotor diffusion as a function of torque.

physics.bio-ph↗

arXiv2008

A quantitative comparison of sRNA-based and protein-based gene regulation

Small, non-coding RNAs (sRNAs) play important roles as genetic regulators in prokaryotes. sRNAs act post-transcriptionally via complementary pairing with target mRNAs to regulate protein expression. We use a quantitative approach to compare and contrast sRNAs with conventional transcription factors (TFs) to better understand the advantages of each form of regulation. In particular, we calculate the steady-state behavior, noise properties, frequency-dependent gain (amplification), and dynamical response to large input signals of both forms of regulation. While the mean steady-state behavior of sRNA-regulated proteins exhibits a distinctive tunable threshold-linear behavior, our analysis shows that transcriptional bursting leads to significantly higher intrinsic noise in sRNA-based regulation than in TF-based regulation in a large range of expression levels and limits the ability of sRNAs to perform quantitative signaling. Nonetheless, we find that sRNAs are better than TFs at filtering noise in input signals. Additionally, we find that sRNAs allow cells to respond rapidly to large changes in input signals. These features suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. This functional niche is consistent with the widespread appearance of sRNAs in stress-response and quasi-developmental networks in prokaryotes.

q-bio.MN↗

arXiv2008

Exponential sensitivity of noise-driven switching in genetic networks

Cells are known to utilize biochemical noise to probabilistically switch between distinct gene expression states. We demonstrate that such noise-driven switching is dominated by tails of probability distributions and is therefore exponentially sensitive to changes in physiological parameters such as transcription and translation rates. However, provided mRNA lifetimes are short, switching can still be accurately simulated using protein-only models of gene expression. Exponential sensitivity limits the robustness of noise-driven switching, suggesting cells may use other mechanisms in order to switch reliably.

q-bio.MN↗

arXiv2008

Self-organized periodicity of protein clusters in growing bacteria

Chemotaxis receptors in E. coli form clusters at the cell poles and also laterally along the cell body, and this clustering plays an important role in signal transduction. Recently, experiments using flourrescence imaging have shown that, during cell growth, lateral clusters form at positions approximately periodically spaced along the cell body. In this paper, we demonstrate within a lattice model that such spatial organization could arise spontaneously from a stochastic nucleation mechanism. The same mechanism may explain the recent observation of periodic aggregates of misfolded proteins in E. coli.

cond-mat.stat-mech↗

arXiv2004

Pattern formation within Escherichia coli: diffusion, membrane attachment, and self-interaction of MinD molecules

In E. coli, accurate cell division depends upon the oscillation of Min proteins from pole to pole. We provide a model for the polar localization of MinD based only on diffusion, a delay for nucleotide exchange, and different rates of attachment to the bare membrane and the occupied membrane. We derive analytically the probability density, and correspondingly the length scale, for MinD attachment zones. Our simple analytical model illustrates the processes giving rise to the observed localization of cellular MinD zones.

q-bio.SC↗

arXiv2003

Flexibility of beta-sheets: Principal-component analysis of database protein structures

Protein folds are built primarily from the packing together of two types of structures: alpha-helices and beta-sheets. Neither structure is rigid, and the flexibility of helices and sheets is often important in determining the final fold ({\it e.g.}, coiled coils and beta-barrels). Recent work has quantified the flexibility of alpha-helices using a principal-component analysis (PCA) of database helical structures (Emberly, 2003). Here, we extend the analysis to beta-sheet flexibility using PCA on a database of beta-sheet structures. For sheets of varying dimension and geometry, we find two dominant modes of flexibility: twist and bend. The distributions of amplitudes for these modes are found to be Gaussian and independent, suggesting that the PCA twist and bend modes can be identified as the soft elastic normal modes of sheets. We consider the scaling of mode eigenvalues with sheet size and find that parallel beta-sheets are more rigid than anti-parallel sheets over the entire range studied. Lastly, we discuss the application of our PCA results to modeling and design of beta-sheet proteins.

cond-mat.soft↗

arXiv2003

Statistical mechanics of RNA folding: importance of alphabet size

We construct a minimalist model of RNA secondary-structure formation and use it to study the mapping from sequence to structure. There are strong, qualitative differences between two-letter and four or six-letter alphabets. With only two kinds of bases, there are many alternate folding configurations, yielding thermodynamically stable ground-states only for a small set of structures of high designability, i.e., total number of associated sequences. In contrast, sequences made from four bases, as found in nature, or six bases have far fewer competing folding configurations, resulting in a much greater average stability of the ground state.

cond-mat.stat-mech↗

arXiv2002

Local moment formation in quantum point contacts

Spin-density-functional theory of quantum point contacts (QPCs) reveals the formation of a local moment with a net of one electron spin in the vicinity of the point contact - supporting the recent report of a Kondo effect in a QPC. The hybridization of the local moment to the leads decreases as the QPC becomes longer, while the onsite Coulomb-interaction energy remains almost constant.

cond-mat.mes-hall↗

arXiv2002

Flexibility of $α$-helices: Results of a statistical analysis of database protein structures

$α$-helices stand out as common and relatively invariant secondary structural elements of proteins. However, $α$-helices are not rigid bodies and their deformations can be significant in protein function ({\it e.g.} coiled coils). To quantify the flexibility of $α$-helices we have performed a structural principal-component analysis of helices of different lengths from a representative set of protein folds in the Protein Data Bank. We find three dominant modes of flexibility: two degenerate bend modes and one twist mode. The data are consistent with independent Gaussian distributions for each mode. The mode eigenvalues, which measure flexibility, follow simple scaling forms as a function of helix length. The dominant bend and twist modes and their harmonics are reproduced by a simple spring model, which incorporates hydrogen-bonding and excluded volume. As an application, we examine the amount of bend and twist in helices making up several coiled-coil proteins. Incorporation of $α$-helix flexibility into structure refinement and design is discussed.

cond-mat.stat-mech↗

arXiv2002

Kondo model for the "0.7 anomaly" in transport through a quantum point contact

Experiments on quantum point contacts have highlighted an anomalous conductance plateau at $0.7 (2e^2/h)$, with features suggestive of the Kondo effect. Here we present an Anderson model for transport through a point contact which we analyze in the Kondo limit. Hybridization to the band increases abruptly with energy but decreases with valence, so that the background conductance and the Kondo temperature $T_K$ are dominated by different valence transitions. This accounts for the high residual conductance above $T_K$. A spin-polarized current is predicted for Zeeman splitting $g^* μ_B B > k_B T_K,k_BT$.

cond-mat.mes-hall↗

arXiv2002

Ground-state energy and spin in disordered quantum dots

We investigate the ground-state energy and spin of disordered quantum dots using spin-density-functional theory. Fluctuations of addition energies (Coulomb-blockade peak spacings) do not scale with average addition energy but remain proportional to level spacing. With increasing interaction strength, the even-odd alternation of addition energies disappears, and the probability of non-minimal spin increases, but never exceeds 50%. Within a two-orbital model, we show that the off-diagonal Coulomb matrix elements help stabilize a ground state of minimal spin.

cond-mat.mes-hall↗

arXiv2001

Coordinated Slowing of Metabolism in Enteric Bacteria under Nitrogen Limitation: A Perspective

It is natural to ask how bacteria coordinate metabolism when depletion of an essential nutrient limits their growth, and they must slow their entire rate of biosynthesis. A major nutrient with a fluctuating abundance is nitrogen. The growth rate of enteric bacteria under nitrogen-limiting conditions is known to correlate with the internal concentration of free glutamine, the glutamine pool. Here we compare the patterns of utilization of L-glutamine and L-glutamate, the two central intermediates of nitrogen metabolism. Monomeric precursors of all of the cell's macromolecules -- proteins, nucleic acids, and surface polymers -- require the amide group of glutamine at the first dedicated step of biosynthesis. This is the case even though only a minority (~12%) of total cell nitrogen derives from glutamine. In contrast, the amino group of glutamate, which provides the remainder of cell nitrogen, is generally required late in biosynthetic pathways, e.g. in transaminase reactions for amino acid synthesis. We propose that the pattern of glutamine dependence coordinates the decrease in biosynthesis under conditions of nitrogen limitation. Hence, the glutamine pool plays a global regulatory role in the cell.

physics.bio-ph↗

arXiv2001

Identifying Proteins of High Designability via Surface-Exposure Patterns

Using an off-lattice model, we fully enumerate folded conformations of polypeptide chains of up to N = 19 monomers. Structures are found to differ markedly in designability, defined as the number of sequences with that structure as a unique lowest-energy conformation. We find that designability is closely correlated with the pattern of surface exposure of the folded structure. For longer chains, complete enumeration of structures is impractical. Instead, structures can be randomly sampled, and relative designability estimated either from designability within the random sample, or directly from surface-exposure pattern. We compare the surface-exposure patterns of those structures identified as highly designable to the patterns of naturally occurring proteins.

cond-mat.soft↗

arXiv2001

Temperature Dependent Suppression of Conductance in Quantum Wires: Anomalous Activation Energy from Pinning of the Band Edge

For unpolarized electrons in a clean quantum wire, density functional theory reveals a thermally activated suppression of conductance. The activation temperature T_A grows slowly (roughly quadratically) with gate voltage due to pinning of the band edge at the chemical potential. Similar results were obtained experimentally by Kristensen et al. [Phys. Rev. B62, 10950 (2000)] for the temperature dependence of the anomalous conductance plateau near 0.7 (2e^2/h) in a quantum point contact.

cond-mat.mes-hall↗

arXiv2000

Symmetry and designability for lattice protein models

Native protein folds often have a high degree of symmetry. We study the relationship between the symmetries of native proteins, and their designabilities -- how many different sequences encode a given native structure. Using a two-dimensional lattice protein model based on hydrophobicity, we find that those native structures that are encoded by the largest number of different sequences have high symmetry. However only certain symmetries are enhanced, e.g. x/y-mirror symmetry and $180^o$ rotation, while others are suppressed. If it takes a large number of mutations to destabilize the native state of a protein, then, by definition, the state is highly designable. Hence, our findings imply that insensitivity to mutation implies high symmetry. It appears that the relationship between designability and symmetry results because protein substructures are also designable. Native protein folds may therefore be symmetric because they are composed of repeated designable substructures.

cond-mat.stat-mech↗