Advances in Colloid and Interface Science (v.232, #C)

Attractive ion–ion correlation forces and the dielectric approximation by Luis Pegado; Bo Jönsson; Håkan Wennerström (1-8).
We analyze the classical problem of the interaction between two charged surfaces separated by a solution containing neutralizing counter-ions. The focus is on obtaining a description where the solvent is treated explicitly rather than through a dielectric approximation as is conventionally done. We summarize the results of three papers where we have used a Stockmayer fluid model in Monte Carlo simulations. It is shown that the attractive ion–ion correlation mechanism is also operating when the solvent is described explicitly. There appears an oscillatory component to the force, but when this is accounted for, there is a semi-quantitative agreement between the continuum model and the model with explicit solvent. The properties of the continuum model can be reached in a molecular system by making the solvent molecules much smaller than the ions. It is demonstrated that having an explicit solvent model makes the analysis of force mechanisms more delicate due to the interplay between several different microscopic contributions to the force. Finally, it is argued that the agreement between the forces calculated using the continuum and the explicit solvent models, respectively, has as its basis the circumstance that the force between the surfaces is mainly caused by long-range ion–ion interactions, for which the dielectric approximation is most adequate. This argument applies equally well to an aqueous system as to the Stockmayer fluid.
Keywords: Ion–ion correlations; Dielectric approximation; Double layer forces; Molecular solvent; Monte Carlo simulations;

The effect of multivalent cations and Tau on paclitaxel-stabilized microtubule assembly, disassembly, and structure by Cyrus R. Safinya; Peter J. Chung; Chaeyeon Song; Youli Li; Kai K. Ewert; Myung Chul Choi (9-16).
In this review we describe recent studies directed at understanding the formation of novel nanoscale assemblies in biological materials systems. In particular, we focus on the effects of multivalent cations, and separately, of microtubule-associated protein (MAP) Tau, on microtubule (MT) ordering (bundling), MT disassembly, and MT structure. Counter-ion directed bundling of paclitaxel-stabilized MTs is a model electrostatic system, which parallels efforts to understand MT bundling by intrinsically disordered proteins (typically biological polyampholytes) expressed in neurons. We describe studies, which reveal an unexpected transition from tightly spaced MT bundles to loose bundles consisting of strings of MTs as the valence of the cationic counter-ion decreases from Z = 3 to Z = 2. This transition is not predicted by any current theories of polyelectrolytes. Notably, studies of a larger series of divalent counter-ions reveal strong ion specific effects. Divalent counter-ions may either bundle or depolymerize paclitaxel-stabilized MTs. The ion concentration required for depolymerization decreases with increasing atomic number. In a more biologically related system we review synchrotron small angle x-ray scattering (SAXS) studies on the effect of the Tau on the structure of paclitaxel-stabilized MTs. The electrostatic binding of MAP Tau isoforms leads to an increase in the average radius of microtubules with increasing Tau coverage (i.e. a re-distribution of protofilament numbers in MTs). Finally, inspired by MTs as model nanotubes, we briefly describe other more robust lipid-based cylindrical nanostructures, which may have technological applications, for example, in drug encapsulation and delivery.Counter-ion directed bundling of paclitaxel-stabilized microtubules is a model electrostatic system, which parallels efforts to understand microtubule bundling by intrinsically disordered proteins expressed in neurons. Divalent cations Ba2 +, Sr2 + and Ca2 + induce string-like bundling. Unexpectedly, a significant number of divalent cations, including biological ions Mg2 +, Mn2 +, and Zn2 +, depolymerize paclitaxel-stabilized microtubules in an ion-specific manner.Display Omitted
Keywords: Microtubule; Multivalent counter-ions; Microtubule-associated protein Tau; Intrinsically disordered proteins; Correlated ion density fluctuations; Ion specific effects;

A review of immune amplification via ligand clustering by self-assembled liquid–crystalline DNA complexes by Ernest Y. Lee; Calvin K. Lee; Nathan W. Schmidt; Fan Jin; Roberto Lande; Tine Curk; Daan Frenkel; Jure Dobnikar; Michel Gilliet; Gerard C.L. Wong (17-24).
We examine how the interferon production of plasmacytoid dendritic cells is amplified by the self-assembly of liquid–crystalline antimicrobial peptide/DNA complexes. These specialized dendritic cells are important for host defense because they quickly release large quantities of type I interferons in response to infection. However, their aberrant activation is also correlated with autoimmune diseases such as psoriasis and lupus. In this review, we will describe how polyelectrolyte self-assembly and the statistical mechanics of multivalent interactions contribute to this process. In a more general compass, we provide an interesting conceptual corrective to the common notion in molecular biology of a dichotomy between specific interactions and non-specific interactions, and show examples where one can construct exquisitely specific interactions using non-specific interactions.Display Omitted
Keywords: Innate immunity; TLR9; Polyelectrolytes; Statistical mechanics; Multivalency; SAXS;

Lipoprotein binding to anionic biopolyelectrolytes and the effect of glucose on nanoplaque formation in arteriosclerosis and Alzheimer's disease by G. Siegel; F.H.M.E. Mockenhaupt; A.-L. Behnke; E. Ermilov; K. Winkler; A.R. Pries; M. Malmsten; R. Hetzer; R. Saunders; B. Lindman (25-35).
Arteriosclerosis with its clinical sequelae (cardiac infarction, stroke, peripheral arterial occlusive disease) and vascular/Alzheimer dementia not only result in far more than half of all deaths but also represent dramatic economic problems. The reason is, among others, that diabetes mellitus is an independent risk factor for both disorders, and the number of diabetics strongly increases worldwide. More than one-half of infants in the first 6 months of life have already small collections of macrophages and macrophages filled with lipid droplets in susceptible segments of the coronary arteries. On the other hand, the authors of the Bogalusa Heart Study found a strong increase in the prevalence of obesity in childhood that is paralleled by an increase in blood pressure, blood lipid concentration, and type 2 diabetes mellitus. Thus, there is a clear linkage between arteriosclerosis/Alzheimer's disease on the one hand and diabetes mellitus on the other hand. Furthermore, it has been demonstrated that distinct apoE isoforms on the blood lipids further both arteriosclerotic and Alzheimer nanoplaque formation and therefore impair flow-mediated vascular reactivity as well. Nanoplaque build-up seems to be the starting point for arteriosclerosis and Alzheimer's disease in their later full clinical manifestation.In earlier work, we could portray the anionic biopolyelectrolytes syndecan/perlecan as blood flow sensors and lipoprotein receptors in cell membrane and vascular matrix. We described extensively molecular composition, conformation, form and function of the macromolecule heparan sulfate proteoglycan (HS-PG). In two supplementary experimental settings (ellipsometry, myography), we utilized isolated HS-PG for in vitro nanoplaque investigations and isolated human coronary artery segments for in vivo tension measurements.With the ellipsometry-based approach, we were successful in establishing a direct connection on a molecular level between diabetes mellitus on the one side and arteriosclerosis/Alzheimer's disease on the other side. Application of glucose at a concentration representative for diabetics and leading to glycation of proteins and lipids, entailed a significant increase in arteriosclerotic and Alzheimer nanoplaque formation. IDLapoE4/E4 was by far superior to IDLapoE3/E3 in plaque build-up, both in diabetic and non-diabetic patients. Recording vascular tension of flow-dependent reactivity in blood substitute solution and under application of different IDLapoE isoforms showed an impaired vasorelaxation for pooled IDL and IDLapoE4/E4, thus confirming the ellipsometric investigations. Incubation in IDLapoE0/E0 (apoE “knockout man”), however, resulted in a massive flow-mediated contraction, also complemented by strongly aggregated nanoplaques.In contrast, HDL was shown to present a powerful protection against nanoplaque formation on principle, both in the in vitro model and the in vivo scenario on the endothelial cell membrane. The competitive interplay with LDL is highlighted through the flow experiment, where flow-mediated, HDL-induced vasodilatation remains untouched by additional incubation with LDL. This is due to the four times higher affinity for the proteoglycan receptor of HDL as compared to LDL.Taken together, the studies demonstrate that while simplistic, the ellipsometry approach and the endothelial-mimicking proteoglycan-modified surfaces provide information on the initial steps of lipoprotein-related plaque formation, which correlates with findings on endothelial cells and blood vessels, and afford insight into the role of lipoprotein deposition and exchange phenomena at the onset of these pathophysiologies.Display Omitted
Keywords: Diabetes mellitus and Alzheimer's disease; HS-PG flow sensor and lipoprotein receptor; Glucose and nanoplaque formation; IDLapoE3/E3 and IDLapoE4/E4 isoforms; β-amyloid (1–42); HDL protection;

Multiscale coarse-grained modelling of chromatin components: DNA and the nucleosome by Nikolay Korolev; Lars Nordenskiöld; Alexander P. Lyubartsev (36-48).
To model large biomolecular systems, such as cell and organelles an atomistic description is not currently achievable and is not generally practical. Therefore, simplified coarse-grained (CG) modelling becomes a necessity. One of the most important cellular components is chromatin, a large DNA–protein complex where DNA is highly compacted. Recent progress in coarse graining modelling of the major chromatin components, double helical DNA and the nucleosome core particle (NCP) is presented. First, general principles and approaches allowing rigorous bottom-to-top generation of interaction potentials in the CG models are presented. Then, recent CG models of DNA are reviewed and their adequacy is benchmarked against experimental data on the salt dependence of DNA flexibility (persistence length). Furthermore, a few recent CG models of the NCP are described and their application for studying salt-dependent NCP–NCP interaction is discussed. An example of a multiscale approach to CG modelling of chromatin is presented where interactions and self-assembly of thousands of NCPs in solution are observed.Display Omitted
Keywords: Macromolecular assembly; DNA condensation; Polyelectrolytes; Computer simulations; Inverse Monte Carlo;

Nucleic acids are biopolymers that carry genetic information and are also involved in various gene regulation functions such as gene silencing and protein translation. Because of their negatively charged backbones, nucleic acids are polyelectrolytes. To adequately understand nucleic acid folding and function, we need to properly describe its i) polymer/polyelectrolyte properties and ii) associating ion atmosphere. While various theories and simulation models have been developed to describe nucleic acids and the ions around them, many of these theories/simulations have not been well evaluated due to complexities in comparison with experiment. In this review, I discuss some recent experiments that have been strategically designed for straightforward comparison with theories and simulation models. Such data serve as excellent benchmarks to identify limitations in prevailing theories and simulation parameters.Display Omitted
Keywords: Nucleic acids; Polymer theory; Polyelectrolytes; Ion atmosphere; Poisson–Boltzmann theory; Benchmarking;

This review addresses the recent research progress in introducing and elaborating a novel approach to controlled polymer self-assembly into stable nanoparticles using pH-responsive thermosensitive homopolymer polyelectrolytes. Interesting aspect of this approach is that stable polymeric nanoparticles are formed from homopolymers of one type only and without any assembly-triggering additives. The process of their formation can be monitored online e.g. by light scattering and particle size can be finely custom tuned. Obtained nanoparticles have interesting properties and are very stable over long periods of time and over a broad range of salt concentrations including physiological conditions. Much effort was devoted not only to finding optimum experimental protocols and to characterizing resulting nanoparticles in detail, but also to understanding physical processes behind these successful protocols.Display Omitted
Keywords: Self-assembly; Poly(carboxylic acid); Polyelectrolyte; Thermosensitive; Nanoparticle; pH-responsive;

In a living cell, long genomic DNA is strongly compacted and exists in the environment characterized by a dense macromolecular crowding, high concentrations of mono- and divalent cations, and confinement of ca. 10 μm size surrounded by a phospholipid membrane. Experimental modelling of such complex biological system is challenging but important to understand spatiotemporal dynamics and functions of the DNA in cell. The accumulated knowledge about DNA condensation/compaction in conditions resembling those in the real cell can be eventually used to design and construct partly functional “artificial cells” having potential applications in drug delivery systems, gene therapy, and production of synthetic cells. In this review, I would like to overview the past progress in our understanding of the DNA conformational behavior and, in particular, DNA condensation/compaction phenomenon and its relation to the DNA biological activity. This understanding was gained by designing relevant experimental models mimicking DNA behavior in the environment of living cell. Starting with a brief summary of classic experimental systems to study DNA condensation/compaction, in later parts, I highlight recent experimental methodologies to address the effects of macromolecular crowding and nanoscale and microscale confinements on DNA conformation dynamics. All the studies are discussed in the light of their relevance to DNA behavior in living cells, and future prospects of the field are outlined.Display Omitted
Keywords: DNA condensation and compaction; Crowding; Confinement; Artificial cell; Single-molecule;

The polymer physics of single DNA confined in nanochannels by Liang Dai; C. Benjamin Renner; Patrick S. Doyle (80-100).
In recent years, applications and experimental studies of DNA in nanochannels have stimulated the investigation of the polymer physics of DNA in confinement. Recent advances in the physics of confined polymers, using DNA as a model polymer, have moved beyond the classic Odijk theory for the strong confinement, and the classic blob theory for the weak confinement. In this review, we present the current understanding of the behaviors of confined polymers while briefly reviewing classic theories. Three aspects of confined DNA are presented: static, dynamic, and topological properties. The relevant simulation methods are also summarized. In addition, comparisons of confined DNA with DNA under tension and DNA in semidilute solution are made to emphasize universal behaviors. Finally, an outlook of the possible future research for confined DNA is given.Display Omitted
Keywords: Polymer physics; DNA; Nanochannel; Confinement; Monte Carlo simulation;

Nucleosome dynamics: Sequence matters by Behrouz Eslami-Mossallam; Helmut Schiessel; John van Noort (101-113).
About three quarter of all eukaryotic DNA is wrapped around protein cylinders, forming nucleosomes. Even though the histone proteins that make up the core of nucleosomes are highly conserved in evolution, nucleosomes can be very different from each other due to posttranslational modifications of the histones. Another crucial factor in making nucleosomes unique has so far been underappreciated: the sequence of their DNA. This review provides an overview of the experimental and theoretical progress that increasingly points to the importance of the nucleosomal base pair sequence. Specifically, we discuss the role of the underlying base pair sequence in nucleosome positioning, sliding, breathing, force-induced unwrapping, dissociation and partial assembly and also how the sequence can influence higher-order structures. A new view emerges: the physical properties of nucleosomes, especially their dynamical properties, are determined to a large extent by the mechanical properties of their DNA, which in turn depends on DNA sequence.Display Omitted
Keywords: Chromatin; Nucleosome; DNA sequence;

Bundling in semiflexible polymers: A theoretical overview by Panayotis Benetatos; YongSeok Jho (114-126).
Supramolecular assemblies of polymers are key modules to sustain the structure of cells and their function. The main elements of these assemblies are charged semiflexible polymers (polyelectrolytes) generally interacting via a long(er)-range repulsion and a short(er)-range attraction. The most common supramolecular structure formed by these polymers is the bundle. In the present paper, we critically review some recent theoretical and computational advances on the problem of bundle formation, and point a few promising directions for future work.Display Omitted
Keywords: Bundles; Semiflexible polymers; Polyelectrolytes; Order parameters; Phase transitions;