Criticality and finite size effects in a simple realistic model of stock market

We discuss a simple model based on the Minority Game which reproduces the main stylized facts of anomalous fluctuations in finance. We present the analytic solution of the model in the thermodynamic limit and show that stylized facts arise only close to a line of critical points with non-trivial properties. By a simple argument, we show that, in Minority Games, the emergence of critical fluctuations close to the phase transition is governed by the interplay between the signal to noise ratio and the system size. These results provide a clear and consistent picture of financial markets as critical systems.Comment: 4 pages, 4 figure

An accurate in vitro model of the E. coli envelope

Gram-negative bacteria are an increasingly serious source of antibiotic-resistant infections, partly owing to their characteristic protective envelope. This complex, 20 nm thick barrier includes a highly impermeable, asymmetric bilayer outer membrane (OM), which plays a pivotal role in resisting antibacterial chemotherapy. Nevertheless, the OM molecular structure and its dynamics are poorly understood because the structure is difficult to recreate or study in vitro. The successful formation and characterization of a fully asymmetric model envelope using Langmuir-Blodgett and Langmuir-Schaefer methods is now reported. Neutron reflectivity and isotopic labeling confirmed the expected structure and asymmetry and showed that experiments with antibacterial proteins reproduced published in vivo behavior. By closely recreating natural OM behavior, this model provides a much needed robust system for antibiotic development

Probing the molecular level details of bacterial outer membrane vesicles and their parent bacteria: A simulation approach

Gram-negative bacteria have an unusual cell envelope that contains an inner cytoplasmic lipid membrane and an outer bacterial lipid membrane. The outer bacterial lipid membrane produces outer membrane vesicles that regulate bacterial pathogenesis processes. The outer membrane vesicles transport virulence factors from bacteria to host cell surfaces and the vesicles then move into the host cell cytosol. Computer simulations were conducted here in this thesis to understand how outer membrane vesicles pass through host cell surfaces independently of any membrane protein effects. The simulations suggest that outer membrane vesicles enter cells via lipidmediated endocytosis processes and interestingly, that the host membrane wrapping interactions depend on the length of the lipopolysaccharide macromolecules. Additional simulations were conducted to understand how polymyxin B1 peptides affect the inner and outer membranes of Gramnegative bacteria and how cohesive intermolecular interactions between lipopolysaccharide lipids can affect the durability of Gram-negative bacterial membranes. The simulation studies are by no means disparate; the simulations provide general insights into disease transmission. The simulations clarify how lipopolysaccharide macromolecules promote the spread of disease and conversely how antibiotics can curb it

To infect or not to infect: molecular determinants of bacterial outer membrane vesicle internalization by host membranes

Outer membrane vesicles (OMVs) are spherical liposomes that are secreted by almost all forms of Gram-negative bacteria. The nanospheres contribute to bacterial pathogenesis by trafficking molecular cargo from bacterial membranes to target cells at the host-pathogen interface. We have simulated the interaction of OMVs with host cell membranes to understand why OMV uptake depends on the length of constituent lipopolysaccharide macromolecules. Using coarse-grained molecular dynamics simulations, we show that lipopolysaccharide lipid length affects OMV shape at the host-pathogen interface: OMVs with long (smooth-type) lipopolysaccharide lipids retain their spherical shape when they interact with host cell membranes, whereas OMVs with shorter (rough-type) lipopolysaccharide lipids distort and spread over the host membrane surface. In addition, we show that OMVs preferentially coordinate domain-favoring ganglioside lipids within host membranes to enhance curvature and affect the local lipid composition. We predict that these differences in shape preservation affect OMV internalization on long timescales: spherical nanoparticles tend to be completely enveloped by host membranes, whereas low sphericity nanoparticles tend to remain on the surface of cells

The role of O-antigen in the response to mechanical stress of the E. coli outer membrane: Insights from coarse-grained MD simulations

Lipopolysaccharide (LPS) is an important component of the outer membrane of Gram-negative bacteria, contributing to the structural integrity of the bacterial cell wall and conferring resistance to chemical attack. The rough variant of LPS contains a conserved lipid A domain and a complete core saccharide section, whereas the smooth variant additionally contains a terminal O-antigen chain. In the following, smooth LPS lipids are simulated in multicomponent membrane models using coarse-grained molecular dynamics. The simulations reveal that the lipid environment of smooth LPS lipids affects the orientation and clustering of their O-antigen chains. When the outer membrane leaflets contain smooth LPS lipids alone, the O-antigen chains are packed tightly, leading to strong cohesive intermolecular interactions. When the outer leaflets incorporate interstitial phospholipids and rough LPS variants, the O-antigen chains are tilted and less tightly bound. The different packing of terminal O-antigen chains affects lipid mobility and the mechanical strength of the Gram-negative membrane models. Gram-negative membranes with outer leaflets of smooth LPS alone can withstand surface tensions (150 mN m–1) that cause the membrane models with rough LPS lipids and comparable phospholipid bilayers to rupture much more readily

Outer membrane proteins OmpA, FhuA, OmpF, EstA, BtuB, and OmpX have unique lipopolysaccharide fingerprints

The outer membrane of Gram-negative bacteria has a highly complex asymmetrical architecture, containing a mixture of phospholipids in the inner leaflet and almost exclusively lipopolysaccharide (LPS) molecules in the outer leaflet. In E. coli, the outer membrane contains a wide range of proteins with a β barrel architecture, that vary in size from the smallest having eight strands to larger barrels composed of 22 strands. Here we report coarse-grained molecular dynamics simulations of six proteins from the E. coli outer membrane OmpA, OmpX, BtuB, FhuA, OmpF, and EstA in a range of membrane environments, which are representative of the in vivo conditions for different strains of E. coli. We show that each protein has a unique pattern of interaction with the surrounding membrane, which is influenced by the composition of the protein, the level of LPS in the outer leaflet, and the differing mobilities of the lipids in the two leaflets of the membrane. Overall we present analyses from over 200 μs of simulation for each protein.</p

Molecular dynamics simulations predict the pathways via which pristine fullerenes penetrate bacterial membranes

Carbon fullerenes are emerging as effective devices for different biomedical applications, including the transportation of nanosized drugs and extraction of harmful oxidants and radicals. It has been proposed that fullerenes could be used as novel antibacterial agents, given the realization that the nanoparticles can kill pathogenic Gram-negative bacteria. To explore this at the molecular level, we simulated C60 fullerenes with bacterial membranes using the coarse-grain molecular dynamics Martini force field. We found that pristine C60 has a limited tendency to penetrate (incomplete core) Re mutant lipopolysaccharide (LPS) leaflets, but the translocation of C60 fullerenes into(complete core) Ra mutant LPS leaflets is not thermodynamically favored. Moreover, we showed that the permeability of the Re LPS bilayers depends sensitively on the system temperature, charge of ambient ions, and prevalence of palmitoyloleoylphosphoethanolamine (POPE) defect domains. The different permeabilities are rationalized in terms of transitory head group pore formation, which underpins the translocation of C60 into the lipid core. The Re LPS lipids readily form transient micropores when they are linked with monovalent cations or when they are heated to a high temperature. POPE lipids are shown to be particularly adept at forming these transient surface cavities, and their inclusion into Re LPS membranes facilitates the formation of particularly large pores that are tunneled by C60 aggregates of a significant size (?5 nm wide). After insertion into the lipid core, the aggregates dissociate, and the disbanded nanoparticles migrate to the interface between separate POPE and LPS domains, where they weaken the boundaries between the coexisting lipid fractions and thereby promote lipid mixing

Interaction of the antimicrobial peptide polymyxin b1 with both membranes of E. coli: a molecular dynamics study

Antimicrobial peptides are small, cationic proteins that can induce lysis of bacterial cells through interaction with their membranes. Different mechanisms for cell lysis have been proposed, but these models tend to neglect the role of the chemical composition of the membrane, which differs between bacterial species and can be heterogeneous even within a single cell. Moreover, the cell envelope of Gram-negative bacteria such as E. coli contains two membranes with differing compositions. To this end, we report the first molecular dynamics simulation study of the interaction of the antimicrobial peptide, polymyxin B1 with complex models of both the inner and outer membranes of E. coli. The results of &gt; 16 micro-seconds of simulation predict that polymyxin B1 is likely to interact with the membranes via distinct mechanisms. The lipopeptides aggregate in the lipopolysaccharide headgroup region of the outer membrane with limited tendency for insertion within the lipid A tails. In contrast, the lipopeptides readily insert into the inner membrane core, and the concomitant increased hydration may be responsible for bilayer destabilization and antimicrobial function. Given the urgent need to develop novel, potent antibiotics, the results presented here reveal key mechanistic details that may be exploited for future rational drug development

Through the lipopolysaccharide glass: a potent antimicrobial peptide induces phase changes in membranes

In the following molecular simulations are used to reveal unexpected behavior within bacterial membranes. We show that lipopolysaccharide molecules found in these membranes form viscous amorphous solids when they are interlinked with monovalent and divalent cations. The bilayers exhibit both liquid and glassy characteristics, due to the co-existence of both liquid and crystalline domains in the bilayer. Polymyxin B1 (PMB1), a potent antimicrobial peptide, is shown to increase order within the LPS bilayers by inducing the formation of crystalline patches. Crucially we are able to decompose the energetics of insertion into their enthalpic and entropic components. The present coarse-grain (CG) molecular dynamics (MD) study provides unprecedented insights into the antibacterial action of antimicrobial peptides, thus paving the way for development of novel therapeutic agents to treat multiple drug resistant Gram-negative bacteria