How the biomimetic assembly of membrane receptors into multivalent domains is regulated by a small ligand

In living cells, communication requires the action of membrane receptors that are activated following very small environmental changes. A binary all-or-nothing behavior follows, making the organism extremely efficient at responding to specific stimuli. Using a minimal system composed of lipid vesicles, chemical models of a membrane receptor and their ligands, we show that bio-mimetic ON/OFF assembly of high avidity, multivalent domains is triggered by small temperature changes. Moreover, the intensity of the ON signal at the onset of the switch is modulated by the presence of small, weakly binding divalent ligands, reminiscent of the action of primary messengers in biological systems. Based on the analysis of spectroscopic data, we develop a mathematical model that rigorously describes the temperature-dependent switching of the membrane receptor assembly and ligand binding. From this we derive an equation that predicts the intensity of the modulation of the ON signal by the ligand-messenger as a function of the pairwise binding parameters, the number of binding sites that it features and the concentration. The behavior of our system, and the model derived, highlight the usefulness of weakly binding ligands in the regulation of membrane receptors and the pitfalls inherent to their binding promiscuity, such as non-specific binding to the membrane. Our model, and the equations derived from it, offer a valuable tool for the study of membrane receptors in both biological and biomimetic settings. The latter can be exploited to program membrane receptor avidity on sensing vesicles, create hierarchical protocell tissues or develop highly specific drug delivery vehicles.

In lipid vesicles near their membrane phase-transition temperature, the presence of a small, weakly binding ligand tips the balance for the assembly of multivalent receptor domains. We recapitulate this behaviour using a global binding-clustering model.     

Application of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry in human metabolomic studies

In this paper several characteristic features of time-of-flight mass spectrometry in coupling with gas chromatography are demonstrated and the parameters are compared to quadrupole mass analyzer. In the second part, the comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry was applied in human metabolomic field, particularly in the determination of pathological markers of Inherited Metabolic Disorders (IMDs).     

Strict and bistrict plus-operators

We consider the theory of operators in spaces with indefinite metric. Strict plus-operators acting between two Krein spaces are considered. A construction showing that, under certain conditions, a strict plus-operator can be considered as a bistrict plus-operator without loss of generality is given.     

Construction of sundials via vectors

A method based on oblique projection is presented for construction of sundials. The derived formulas are classical, but usage of vectors and projections renders a coherent presentation rather than a number of special cases. The presented work is aimed to be useful for those taking a beginning module on vector algebra.     

An elementary algorithm to evaluate trigonometric functions to high precision

Evaluation of the cosine function is done via a simple Cordic-like algorithm, together with a package for handling arbitrary-precision arithmetic in the computer program Matlab. Approximations to the cosine function having hundreds of correct decimals are presented with a discussion around errors and implementation.     

Sticking efficiency of nanoparticles in high-velocity collisions with various target materials

In order to find reliable collector surfaces for the Mesospheric Aerosol – Genesis, Interaction and Composition (MAGIC) sounding rocket experiment, intended to collect atmospheric nanoparticles, the sticking efficiency of nanoparticles was measured on several targets of different materials. The nanoparticles were generated by a molecular beam apparatus in Jena, Germany, by laser ablation (Al₂O₃ particles, diameter 5–50 nm) and by laser pyrolysis (carbon particles, diameter 10–20 nm). In a vacuum environment (>10⁻⁵ mbar) the particles condensed from the gas phase, formed a particle beam, and were accelerated to ∼ ∼1 km/s. The sticking efficiency on the target materials carbon, gold and grease was measured by a microbalance. Results demonstrate moderate to high sticking probabilities. Thus, the capture and retrieval of atmospheric nanoparticles was found to be quantitatively feasible.     

Computation of affinity and selectivity: Binding of 2,4-diaminopteridine and 2,4-diaminoquinazoline inhibitors to dihydrofolate reductases

Binding energy calculations for complexes of mutant and wild-type human dihydrofolate reductases with 2,4-diaminopteridine and 2,4-diaminoquinazoline inhibitors are reported. Quantitative insight into binding energetics of these molecules is obtained from calculations based on force field energy evaluation and thermal sampling by molecular dynamics simulations. The calculated affinity of methotrexate for wild-type and mutant enzymes is reasonably well reproduced. Truncation of the methotrexate glutamate tail results in a loss of affinity by several orders of magnitude. No major difference in binding strength is predicted between the pteridines and the quinazolines, while the N-methyl group present in methotrexate appears to confer significantly stronger binding. The recent improvement, which is used here, of our linear interaction energy method for binding affinity prediction, as well as problems with treating charged and flexible ligands are discussed. This approach should be suitable in a drug discovery context for prediction of binding energies of new inhibitors prior to their synthesis, when some information about the binding mode is available.     

Chaotic particle motion under linear surface waves

We investigate the motion of infinitesimal particles in the flow field inside the fluid under a traveling surface wave. It is shown that, even for two-dimensional waves, a superposition of two or more traveling harmonic waves is enough to generate chaotic particle motion, i.e., Lagrangian chaos. (c) 1996 American Institute of Physics.