Arbitrary self-assembly of peptide extracellular microscopic matrices

Two faces for one matrix: A single bifaceted cyclopeptide block forms highly branched, porous, and intricate fibrillar networks, which span microscopic dimensions and mimic the extracellular matrix to support cell growth and proliferation. The peptide block has two domains connected with triglycine linkers (GGG); the domains consist of positively (blue) and negatively (red) charged heptads that provide interactions between different blocks.     

An apparent violation of microscopic reversibility: mechanisms for ligand substitution reactions of oxorhenium(V) dithiolate complexes

The first theoretical investigation on the mechanism for ligand substitution in five-coordinate square pyramidal oxorhenium dithiolate complexes, CH3ReO(SCH2C6H4S)-X, has been carried out with the Perdew-Burke-Ernzerhof density functional and the Stuttgart relativistic effective-core-potential basis sets. In the mechanism proposed in the experimental kinetic studies, the entering ligand Y attacks the vacant lower axial coordinate site trans to O, and the resulting six-coordinate intermediate rearranges through a turnstile twist (a trigonal prismatic intermediate or transition state) or pentagonal pyramid to allow the leaving ligand X to exit from the same site. These workers proposed this rearrangement to avoid a violation of microscopic reversibility. The computed energy barriers in this reaction pathway show that the turnstile or pentagonal pyramidal transition states are too high in energy to make this pathway accessible. Although the vacant lower axial site in the rhenium complex is the site most easily attacked by Y, transition states for X leaving from the site cis to the attack have quite low energy barriers. Although this direct-exchange mechanism was thought to lead to a violation of microscopic reversibility, we show that these direct-exchange pathways provide low-energy routes for ligand exchange and clarify this apparent violation of microscopic reversibility. Furthermore, computed results of different entering and leaving ligand pairs are analyzed for their effect on the choice of reaction pathways. In the direct-exchange mechanism, the replacement of 4-tBu-pyridine by PPhMe2 is monophasic without an intermediate, but the replacement of PPh3 by PPhMe2 is biphasic (proceeds by a two-stage pathway) and generates the observed intermediate, an isomer of product. These predictions are completely consistent with the observed experimental phenomena. The accuracy of the particular functional/basis set used for the study is compared to 10 functionals in 19 basis sets and to large basis set coupled cluster calculations on model systems.     

Testing for violations of microscopic reversibility in ATP-sensitive potassium channel gating

In pancreatic beta cells, insulin secretion is tightly controlled by the cells' metabolic state via the ATP-sensitive potassium (KATP) channel. ATP is a key mediator in this signaling process, where its role as an inhibitor of KATP channels has been extensively studied. Since the channel contains an ATPase as an accessory subunit, the possibility that ATP hydrolysis mediates KATP channel opening has also been proposed. However, a rigorous test of coupling between ATP hydrolysis and channel gating has not previously been performed. In the present work, we examine whether KATP channel gating obeys detailed balance in order to determine whether ATP hydrolysis is strongly coupled to the gating of the KATP channel. Single-channel records were obtained from inside-out patches of transiently transfected HEK-293 cells. Channel activity in membrane patches with exactly one channel shows no violations of microscopic reversibility. Although KATP channel gating shows long closed times on the time scale where ATP hydrolysis takes place, the time symmetry of channel gating indicates that it is not tightly coupled to ATP hydrolysis. This lack of coupling suggests that channel gating operates close to equilibrium; although detailed balance is not expected to hold for ATP hydrolysis, it still does so in channel gating. On the basis of these results, the function of the ATPase active site in channel gating may be to sense nucleotides by differential binding of ATP and ADP, rather than to drive a thermodynamically unfavorable conformational change.     

Physical mechanisms and biological significance of supramolecular protein self-assembly

In living cells, chemical reactions of metabolism, information processing, growth and development are organized in a complex network of interactions. At least in part, the organization of this network is accomplished as a result of physical assembly by supramolecular scaffolds. Indeed, most proteins function in cells within the context of multimeric or supramolecular assemblies. With the increasing availability of atomic structures and molecular thermodynamics, it is possible to recast the problem of non-covalent molecular self-assembly from a unified perspective of structural thermodynamics and kinetics. Here, we present a generalized theory of self-assembly based on Wegner's kinetic model and use it to delineate three physical mechanisms of self-assembly: as limited by association of assembly units (nucleation), by association of monomers (isodesmic), and by conformational reorganization of monomers that is coupled to assembly (conformational). Thus, we discuss actin, tubulin, clathrin, and the capsid of icosahedral cowpea chlorotic mottle virus with respect to assembly of architectural scaffolds that perform largely mechanical functions, and pyruvate dehydrogenase, and RING domain proteins PML, arenaviral Z, and BRCA1:BARD1 with regard to assembly of supramolecular enzymes with metabolic and chemically directive functions. In addition to the biological functions made possible by supramolecular self-assembly, such as mesoscale mechanics of architectural scaffolds and metabolic coupling of supramolecular enzymes, we show that the physical mechanisms of self-assembly and their structural bases are biologically significant as well, having regulatory roles in both formation and function of the assembled structures in health and disease.     

The connection between the second law of thermodynamics and the principle of microscopic reversibility

The connection between the second law of thermodynamics and the principle of microscopic reversibility is studied with mathematical rigor. It is shown that a kinetic scheme adhering to microscopic reversibility necessarily obeys the second law. In addition, it is also proved that any reaction linearly independent from the others must be microscopically reversible. This condition is not necessary for reactions whose stoichiometry can be given as a linear combination of others. An example is given to prove this fact.     

Test of the procedure for obtaining detailed endothermic rate constants from microscopic reversibility

Experimental data concerning the effect of varying reagent vibrational, rotational and translational energy on the rates of endothermic reactions can be obtained from the application of microscopic reversibility to the corresponding exothermic processes. A 3D classical trajectory computation has been performed to test this procedure. On the basis of this study we conclude that the ‘triangle plots’ of endothermic detailed rate constants published previously can be depended on to 5–10% theoretical accuracy (expressed as a percentage of the maximum endothermic rate constant).     

Violation of microscopic reversibility and the use of reverse quais-classical trajectories for calculating reaction cross sections

In order to calculate the transition probabilities (or cross sections) for reactive collisions, such as A + BC(ν, j)→ AB(ν′, j) + C, using the quasi-classical trajectory method, one quantizes the internal energy of the reagents and in addition adopts some algorithm for calculating the internal quantum numbers of the products. A serious consequence of this procedure is that the quasi-classical results do not obey microscopic reversibility. It is shown that for the collinear F + H₂(ν = 0) → FH(ν = 2, 3)+ H reaction (and its D₂ counterpart), the quasi-classical trajectory probabilities for the reverse reaction not only differ substantially from the forward ones but in general are in much better agreement with accurate quantum calculations. A similar situation was found for the collinear H + H₂(0) → H₂(1) + H reaction. We suggest that in doing quasi-classical calculations, the reverse of the process of interest should also be considered. Comparison of forward and reverse quasi-classical collinear calculations with accurate collinear quantum results could give an indication of whether forward or reverse calculations should be used for the three-dimensional case.     

Tunable instability mechanisms of polymer thin films by molecular self-assembly

Incorporation of a block copolymer into a thin polymer film is observed to alter both the rate and mechanism by which the film dewets from an immiscible polymer substrate. Films with little or no copolymer dewet by classical nucleation and growth of circular holes, and the dewetting rate decreases with increasing copolymer concentration. Increasing the copolymer content at constant film thickness generates copolymer micelles that adsorb/aggregate along the polymer/polymer interface and promote nonclassical dewetting fluctuations similar in appearance to spinodal dewetting. At higher copolymer concentrations, dewetting proceeds after a lengthy induction period by the nucleation and growth of flower-shaped holes suggestive of film pinning or viscous fingering. Atomic force microscopy of the polymer/polymer interface after removal of the top film by selective dissolution reveals substantial structural development due to copolymer self-assembly.     

A hybrid approach for microscopic properties and self-assembly of dendrimers between two hard walls

Dendrimers are of interest in a number of applications and theoretical studies due to their interesting and complex architectures. We use a hybrid approach to investigate the microstructure of hard dendrimers and self-assembly of diblock dendrimers confined between two hard walls. In the hybrid approach, a single-chain Monte Carlo simulation is used to evaluate the ideal-gas contribution of the Helmholtz energy and a density functional theory is employed to calculate the excess Helmholtz energy. In our calculations, a coarse-grained model is used to represent the dendrimers of generations 1-4. The effects of generation and bulk packing fraction on the microscopic properties of the hard dendrimers are explored. With the increase of generations, the complexity of the dendritic architecture increases. Accordingly, the depletion effect becomes stronger with the generation at etabulk = 0.1. Furthermore, it is found that the more complex the molecular architecture and the higher the molecular stiffness, the smaller is the partitioning coefficient of confined dendrimers. In addition, we also investigate the effects of the width of the slit and the interaction (epsilon*AA) between hydrophilic segments on the self-assembly of diblock dendrimers in the slit. With the increase of epsilon*AA, we observe that the curves of average packing fraction of the dendrimers in the slit exist an abrupt jump, which corresponds to the first-order phase transition from a disordered state to a lamellar ordered structure. In the slit of H = 11sigma, it is at epsilon*AA = 8 rather than epsilon*AA = 10 or epsilon*AA = 12 that the minimum critical bulk packing fraction appears. This observation is distinctively different from the case of self-assembly of rod-like molecules in the slit, where the critical bulk concentration increases with the decrease of the head-head interaction linearly.     

Phase diagrams,mechanisms and unique characteristics of alternating-structured polymer self-assembly via simulations

Alternating-structured polymers(ASPs), like alternating copolymers, regular multiblock copolymers and polycondensates, are very important polymer structures with broad applications in photoelectric materials. However, their self-assembly behaviors,especially the self-assembly of alternating copolymers, have not been clearly studied up to now. Meanwhile, the unique characteristics therein have not been systematically disclosed yet by both experiments and theories. Herein, we have performed a systematic simulation study on the self-assembly of ASPs with two coil alternating segments in solution through dissipative particle dynamics(DPD) simulations. Several morphological phase diagrams were constructed as functions of different impact parameters. Diverse self-assemblies were observed, including spherical micelles, micelle networks, worm-like micelles, disklike micelles, multimicelle aggregates, bicontinuous micelles, vesicles, nanotubes and channelized micelles. Furthermore, a morphological evolutionary roadmap for all these self-assemblies was constructed, along with which the detailed molecular packing models and self-assembly mechanisms for each aggregate were disclosed. The ASPs were found to adopt a folded-chain mechanism in the self-assemblies. Finally, the unique characteristics for the self-assembly of alternating copolymers were revealed especially, including(1) ultra-fine and uniform feature sizes of the aggregates;(2) independence of self-assembled structures from molecular weight and molecular weight distribution;(3) ultra-small unimolecular aggregates. We believe the current work is beneficial for understanding the self-assembly of alternating structured polymers in solution and can serve as a guide for the further experiments.     

Reinforced self-assembly of hexa-peri-hexabenzocoronenes by hydrogen bonds: from microscopic aggregates to macroscopic fluorescent organogels

Hexa-peri-hexabenzocoronene derivatives (HBCs) that have hydrogen-bonding functionalities (either amido or ureido groups) adjacent to the aromatic cores have been synthesized to study the effects of intracolumnar hydrogen bonds on the self-assembly behavior of HBCs. The hydrogen bonds effectively increased the aggregation tendency of these compounds in solution. In the bulk state, the typical columnar supramolecular arrangement of HBCs was either stabilized substantially (1 a, 1 b, 2 a, and 2 b), or suppressed by dominant hydrogen-bonding interactions (3). For some of the compounds (1 a, 2 a, and 2 b), the supramolecular arrangement adopted in the liquid-crystalline state was even retained after annealing, presumably owing to the reinforcement of the pi-stacking interactions by the hydrogen bonds. Additionally, the combined effect of the hydrogen bonds and pi-stacking of the aromatic moieties led to the formation of fluorescent organogels, whereby some derivatives were further investigated as novel low molecular-mass organic gelators (LMOGs).     

Issues of microscopic reversibility and an isomeric intermediate in ligand substitution reactions of five-coordinate oxorhenium(V) dithiolate complexes.

Ligand substitution reactions between five-coordinate oxorhenium(V) dithiolates, [CH(3)ReO(SCH(2)C(6)H(4)S)X], or MeReO(mtp)X, and entering ligands Y have been studied; Y is a phosphine and X is a phosphine (usually) or a pyridine. Many of them occur in two distinct stages, and other two-stage reactions merge to a single kinetic term when the successive rate constants are quite different in value. An intermediate can be detected directly by electronic and NMR spectroscopy. Just for phosphines, the range of rate constants is remarkably large; in the first stage, k spans the range 10(-)(4)-10(1) L mol(-)(1) s(-)(1) at 25 degrees C in benzene; in the second, which also shows a first-order dependence on the concentration of the entering ligand, the range is 10(-)(4)-10(3) L mol(-)(1) s(-)(1). Spectroscopic evidence shows that the intermediate has the same composition as the product; the metastable form is designated as MeReO(mtp)Y. The structures of all the isolated products MeReO(mtp)Y have a single stereochemistry: Me and -SCH(2) lie in trans positions, as do Y and -SAr. This structure is believed to be reversed in the transient, Y and -SCH(2) occupying trans positions. Further support for this assignment comes from the (31)P splitting of the (1)H NMR spectrum, where additional coupling indicates unusual four-bond coupling from a W-pattern of the hydrogen and phosphorus atoms. The intermediate does not undergo an intramolecular rearrangement to the final product; instead, it reacts with a ligand of the same type in an intermolecular reaction leading to rearrangement. The activation parameters were determined for selected reactions, and the results support a mechanism with considerable associative character; DeltaS() values are ca. -125 J K(-)(1) mol(-)(1). Because ligand Y must enter the coordination sphere from the vacant coordination position trans to the Re=O group, a means must be devised for the leaving group X to gain that position. To account for the intervention of the isomer while honoring the principle of microscopic reversibility, two mechanisms are proposed. One involves a C(3) ("turnstile") rotation of a specific group of three ligands in the six-coordinate transition state. Turnstile rotation of the groups X, Me, and Y can accomplish the needed transposition; the transition state passes through an approximate trigonal prismatic configuration, giving rise to a different and less stable isomer. The alternative mechanism, which may more easily accommodate data for Y = Me(2)bpy, involves rearrangement of the common octahedral intermediate to a pentagonal pyramid. The arrangement of ligands in the intermediate, governed by their sizes, determines that isomerization accompanies product formation. Following either rearrangement, a second reaction, between MeReO(SCH(2)C(6)H(4)S)Y and Y, then ensues by the same mechanism. The second rearrangement process then generates the more stable isomer of the product. Results are also presented from a study of monomerization of the dimeric rhenium species, [MeReO(mtp)](2), with phosphines(X) of various size and basicity. The results support a mechanism with two intermediates on the pathway to MeReO(mtp)X.     

Water under temperature gradients: polarization effects and microscopic mechanisms of heat transfer

We report non-equilibrium molecular dynamics simulations (NEMD) of water under temperature gradients using a modified version of the central force model (MCFM). This model is very accurate in predicting the equation of state of water for a wide range of pressures and temperatures. We investigate the polarization response of water to thermal gradients, an effect that has been recently predicted using Non-Equilibrium Thermodynamics (NET) theory and computer simulations, as a function of the thermal gradient strength. We find that the polarization of the liquid varies linearly with the gradient strength, which indicates that the ratio of phenomenological coefficients regulating the coupling between the polarization response and the heat flux is independent of the gradient strength investigated. This notion supports the NET theoretical predictions. The coupling effect leading to the liquid polarization is fairly strong, leading to polarization fields of ~10(3-6) V m(-1) for gradients of ~10(5-8) K m(-1), hence confirming earlier estimates. Finally we employ our NEMD approach to investigate the microscopic mechanism of heat transfer in water. The image emerging from the computation and analysis of the internal energy fluxes is that the transfer of energy is dominated by intermolecular interactions. For the MCFM model, we find that the contribution from hydrogen and oxygen is different, with the hydrogen contribution being larger than that of oxygen.     

Stability and reversibility of LiBH4

LiBH4 is a complex hydride and exhibits a high gravimetric hydrogen density of 18.5 wt %. Therefore it is a promising hydrogen storage material for mobile applications. The stability of LiBH4 was investigated by pcT (pressure, concentration, and temperature) measurements under constant hydrogen flows and extrapolated to equilibrium. According to the van 't Hoff equation the following thermodynamic parameters are determined for the desorption: enthalpy of reaction DeltarH = 74 kJ mol-1 H2 and entropy of reaction DeltarS = 115 J K-1 mol-1 H2. LiBH4 decomposes to LiH + B + 3/2H2 and can theoretically release 13.9 wt % hydrogen for this reaction. It is shown that the reaction can be reversed at a temperature of 600 degrees C and at a pressure of 155 bar. The formation of LiBH4 was confirmed by XRD (X-ray diffraction). In the rehydrided material 8.3 wt % hydrogen was desorbed in a TPD (temperature-programmed desorption) measurement compared to 10.9 wt % desorbed in the first dehydrogenation.     

Experimental self-assembly: the many facets of self-assembly

The self-assembly of matter is manifested throughout the hierarchy of the universe in a myriad of modes, both biotic and abiotic. It is not only an area of deep interest as a fundamental prerequisite to life, but it is now emerging as a strategy to many new unanticipated synthetic architectures, unique properties and commercial applications. In this issue, 11 authors review recent advances in each of these realms. Considering the vastness of the subject, we have chosen to focus on selected highlights in three general areas, namely: (i) synthesis; (ii) dynamics/characterization/external parameters affecting assembly; and (iii) theoretical/biological perspectives. Current Opinion in Colloid & Interface Science 1999, 4:3–5 Electronic identifier: 1359-0294-004-00003 ©1999 Elsevier Science Ltd. All rights reserved. ISSN 1359-0294