The cytoplasm of living cells: A functional mixture of thousands of components

Inside every living cell is the cytoplasm: a fluid mixture of thousands of different macromolecules, predominantly proteins. This mixture is where most of the biochemistry occurs that enables living cells to function, and it is perhaps the most complex liquid on earth. Here we take an inventory of what is actually in this mixture. Recent genome-sequencing work has given us for the first time at least some information on all of these thousands of components. Having done so we consider two physical phenomena in the cytoplasm: diffusion and possible phase separation. Diffusion is slower in the highly crowded cytoplasm than in dilute solution. Reasonable estimates of this slowdown can be obtained and their consequences explored, for example, monomer-dimer equilibria are established approximately twenty times slower than in a dilute solution. Phase separation in all except exceptional cells appears not to be a problem, despite the high density and so strong protein-protein interactions present. We suggest that this may be partially a byproduct of the evolution of other properties, and partially a result of the huge number of components present.Comment: 11 pages, 1 figure, 1 tabl

Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al

Could humans recognize odor by phonon assisted tunneling?

Our sense of smell relies on sensitive, selective atomic-scale processes that are initiated when a scent molecule meets specific receptors in the nose. However, the physical mechanisms of detection are not clear. While odorant shape and size are important, experiment indicates these are insufficient. One novel proposal suggests inelastic electron tunneling from a donor to an acceptor mediated by the odorant actuates a receptor, and provides critical discrimination. We test the physical viability of this mechanism using a simple but general model. Using values of key parameters in line with those for other biomolecular systems, we find the proposed mechanism is consistent both with the underlying physics and with observed features of smell, provided the receptor has certain general properties. This mechanism suggests a distinct paradigm for selective molecular interactions at receptors (the swipe card model): recognition and actuation involve size and shape, but also exploit other processes.Comment: 10 pages, 1 figur

Oats for Grain, Winter Pasture and Other Uses.

20 p

Barley Production in Texas.

16 p

Partition function of two- and three-dimensional Potts ferromagnets for arbitrary values of q>0

A new algorithm is presented, which allows to calculate numerically the partition function Z_q of the d-dimensional q-state Potts models for arbitrary real values q>0 at any given temperature T with high precision. The basic idea is to measure the distribution of the number of connected components in the corresponding Fortuin-Kasteleyn representation and to compare with the distribution of the case q=1 (graph percolation), where the exact result Z_1=1 is known. As application, d=2 and d=3-dimensional ferromagnetic Potts models are studied, and the critical values q_c, where the transition changes from second to first order, are determined. Large systems of sizes N=1000^2 respectively N=100^3 are treated. The critical value q_c(d=2)=4 is confirmed and q_c(d=3)=2.35(5) is found.Comment: 4 pages, 4 figures, RevTe

Computational Discovery of Hydrogen Bond Design Rules for Electrochemical Ion Separation

Selective ion separation is a major challenge with far-ranging impact from water desalination to product separation in catalysis. Recently introduced ferrocene (Fc)/ferrocenium (Fc⁺) polymer electrode materials have been demonstrated experimentally and theoretically to selectively bind carboxylates over perchlorate through weak C–H···O hydrogen bond (HB) interactions that favor carboxylates, despite the comparable size and charge of the two species. However, practical application of this technology in aqueous environments requires further selectivity enhancement. Using a first-principles discovery approach, we investigate the effect of Fc/Fc⁺ functional groups (FGs) on the selectivity and reversibility of formate–Fc⁺ adsorption with respect to perchlorate in aqueous solution. Our wide design space of 44 FGs enables identification of FGs with higher selectivity and rationalization of trends through electronic energy decomposition analysis or geometric hydrogen bonding analysis. Overall, we observe weaker, longer HBs for perchlorate as compared to formate with Fc⁺. We further identify Fc⁺ functionalizations that simultaneously increase selectivity for formate in aqueous environments but permit rapid release from neutral Fc. We introduce the materiaphore, a 3D abstraction of these design rules, to help guide next-generation material optimization for selective ion sorption. This approach is expected to have broad relevance in computational discovery for molecular recognition, sensing, separations, and catalysis.National Science Foundation (U.S.) (ECCS-1449291

Understanding adhesion at as-deposited interfaces from ab initio thermodynamics of deposition growth: thin-film alumina on titanium carbide

We investigate the chemical composition and adhesion of chemical vapour deposited thin-film alumina on TiC using and extending a recently proposed nonequilibrium method of ab initio thermodynamics of deposition growth (AIT-DG) [Rohrer J and Hyldgaard P 2010 Phys. Rev. B 82 045415]. A previous study of this system [Rohrer J, Ruberto C and Hyldgaard P 2010 J. Phys.: Condens. Matter 22 015004] found that use of equilibrium thermodynamics leads to predictions of a non-binding TiC/alumina interface, despite the industrial use as a wear-resistant coating. This discrepancy between equilibrium theory and experiment is resolved by the AIT-DG method which predicts interfaces with strong adhesion. The AIT-DG method combines density functional theory calculations, rate-equation modelling of the pressure evolution of the deposition environment and thermochemical data. The AIT-DG method was previously used to predict prevalent terminations of growing or as-deposited surfaces of binary materials. Here we extent the method to predict surface and interface compositions of growing or as-deposited thin films on a substrate and find that inclusion of the nonequilibrium deposition environment has important implications for the nature of buried interfaces.Comment: 8 pages, 6 figures, submitted to J. Phys.: Condens. Matte

Osmosis in a minimal model system

Osmosis plays a central role in the function of living and soft matter systems. While the thermodynamics of osmosis is well understood, the underlying microscopic dynamical mechanisms remain the subject of discussion. Unraveling these mechanisms is a crucial prerequisite for eventually understanding osmosis in non-equilibrium systems. Here, we investigate the microscopic basis of osmosis, in a system at equilibrium, using molecular dynamics simulations of a minimal model in which repulsive solute and solvent particles differ only in their interactions with an external potential. For this system, we can derive a simple virial-like relation for the osmotic pressure. Our simulations support an intuitive picture in which the solvent concentration gradient, at osmotic equilibrium, arises from the balance between an outward force, caused by the increased total density in the solution, and an inward diffusive flux caused by the decreased solvent density in the solution. While more complex effects may occur in other osmotic systems, they are not required for a description of the basic physics of osmosis in this minimal model.Comment: 10 pages, 8 figure

Performance of Small Grain Varieties in Texas 1949-57.

20 p