Modeling highly branched structures: Description of the solution structures of dendrimers, polyglycerol, and glycogen

Konkolewicz, Dominik; Perrier, Sébastien; Stapleton, David; Gray‐Weale, Angus

doi:10.1002/polb.22340

Cited by 7 publications

(11 citation statements)

References 96 publications

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“…These included highly simplified inclusion of the enzyme kinetics, of which the understanding has significantly advanced in the intervening decades, and limited account of chain self-avoidance. A reverse Monte-Carlo simulation approach [23] had limitations in the problem of self-avoidance, and was such that the enzyme kinetics were assumed in the model by using actual CLDs (this has led to a useful model for randomly-branched polymers and for interpreting some types of experimental data [24][25][26]). These simulations did not take into account effects such as restricted access to an enzyme in a particular region due to the enzyme being unable to fit into the available space.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Exploring glycogen biosynthesis through Monte Carlo simulation

Zhang

Nada

Tan

et al. 2018

International Journal of Biological Macromolecules

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Glycogen, a complex branched polymer of glucose (average chain length ~10 monomer units), is the blood-sugar reservoir in humans and other animals. Certain aspects of its molecular structure relevant to its biological functions are currently unamenable to experimental exploration. Knowledge of these is needed to develop future models for quantitative data-fitting to obtain mechanistic understanding of the biosynthetic processes that give rise to glycogen structure. Monte Carlo simulations of the biosynthesis of this structure with realistic macromolecular parameters reveal how chain growth and stoppage (the latter assumed to be through both the action of glycogen branching enzyme and other degradative enzymes, and by hindrance) control structural features. The simulated chain-length, pair-distance and radial density distributions agree semi-quantitatively with the limited available data. The simulations indicate that a steady state in molecular structure and size is rapidly obtained, that molecular density reaches a maximum near the center of the particle (not at the periphery, as is the case with dendrimers), and that particle size is controlled by both enzyme activity and hindrance. This knowledge will aid in the understanding of diabetes (loss of blood-sugar control), which has been found to involve subtle differences in glycogen molecular structure.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Exploring glycogen biosynthesis through Monte Carlo simulation

Zhang

Nada

Tan

et al. 2018

International Journal of Biological Macromolecules

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“…However, recent small‐angle X‐ray scattering data of glycogen β‐particles have allowed the application of robust polymer branching models that describe the evolution of branching as a function of particle radius. This has shown that glycogen β‐particles are best described as randomly hyperbranched polymer particles, rather than fractal structures, with a radius of gyration that scales with the logarithm of the molecular weight (i.e., R g ≈ log M ) . This has recently been complemented by Monte Carlo simulations that suggest that glycogen particles have a higher density toward the core of the particles than at the periphery (Figure F) .…”

Section: Structure and Physicochemical Properties Of Glycogen Nanoparmentioning

confidence: 91%

Glycogen as a Building Block for Advanced Biological Materials

2019

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complex drug delivery systems that are challenging to scale up and therefore have limited clinical and commercial translation. Although numerous nanoparticles have been widely developed and used for various applications, including biomedical applications, [2] there is a growing interest in nontoxic and degradable alternatives to first-generation synthetic nanomaterials. Ideally the synthesis of such nanoparticles needs to be cost effective, simple, green, reproducible, scalable, and the constitutive building blocks of the nanoparticles should be nontoxic, functional, biodegradable, and available on a large scale. Naturally occurring nanoparticles could be such a valid alternative. These nanoparticles include intracellular structures, such as magnetosomes [3] and glycogen, and extracellular assemblies such as lipoproteins and viruses. [3] Among these, glycogen is the most abundant and versatile biological nanoparticle, which fulfils the requirements for the fabrication of nanostructured biomaterials. Glycogen is nature's prime nanoparticle that exists in most organisms, from bacteria and archaea to humans, [4,5] as a vital component of the cellular energy machinery. It is a highly branched polysaccharide comprising repeating units of glucose connected by linear α-d-(1,4) glycosidic linkages with α-d-(1,6) branching, structured into roughly spherical nanoparticles that have a high water solubility and molecular weight.The use of polysaccharides as components for advanced materials has been an attractive concept for decades. [6,7] A key motive is that polysaccharides, as a natural biomaterial, are endowed with a level of biodegradability and biocompatibility. In addition, they can be easily modified chemically or biochemically to produce functional derivatives, which are important for various therapeutic applications. [8] The structures of polysaccharides vary considerably but span from linear to highly branched polymers with molecular weights ranging from thousands to millions, composed of mono-or disaccharides, or short-chain oligomers bound together by glycosidic linkages. [9] There is a rich history of research on the use of polysaccharides in a range of therapeutic applications including: i) soft tissue engineering, [10,11] where the materials can be designed to mimic the mechanical properties of the extracellular matrix in the tissue; ii) as drug, protein, or gene delivery systems, [7,12,13] where polysaccharides have a large number of reactive groups [14] that allow for tunable properties [12] such as pH-responsiveness; [15] and iii) as nanoprobes for cellular Biological nanoparticles found in living systems possess distinct molecular architectures and diverse functions. Glycogen is a unique biological polysaccharide nanoparticle fabricated by nature through a bottom-up approach. The biocatalytic synthesis of glycogen has evolved over time to form a nanometer-sized dendrimer-like structure (20-150 nm) with a highly branched surface and a dense core. This makes glycogen markedly different from other natur...

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“…Filippov et al [21] reported a variety of experiments on functionalised commercial oyster glycogen which included some SAXS, though the particles were found to be aggregated. Obtaining SAXS data for glycogen β-particles will allow the test of a structure theory, such as Konkolewicz et al's [22] RBT model. Konkolewicz et al [22] successfully demonstrated the application of RBT to SAXS data of dendrimers, therefore such application on glycogen would provide a direct test of internal structure as to whether the branching is fractal or randomly branched.…”

Section: Introductionmentioning

confidence: 99%

Liver glycogen in type 2 diabetic mice is randomly branched as enlarged aggregates with blunted glucose release

Besford

Zeng

et al. 2015

Glycoconj J

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Glycogen is a vital highly branched polymer of glucose that is essential for blood glucose homeostasis. In this article, the structure of liver glycogen from mice is investigated with respect to size distributions, degradation kinetics, and branching structure, complemented by a comparison of normal and diabetic liver glycogen. This is done to screen for differences that may result from disease. Glycogen α-particle (diameter ∼ 150 nm) and β-particle (diameter ∼ 25 nm) size distributions are reported, along with in vitro γ-amylase degradation experiments, and a small angle X-ray scattering analysis of mouse β-particles. Type 2 diabetic liver glycogen upon extraction was found to be present as large loosely bound, aggregates, not present in normal livers. Liver glycogen was found to aggregate in vitro over a period of 20 h, and particle size is shown to be related to rate of glucose release, allowing a structure-function relationship to be inferred for the tissue specific distribution of particle types. Application of branching theories to small angle X-ray scattering data for mouse β-particles revealed these particles to be randomly branched polymers, not fractal polymers. Together, this article shows that type 2 diabetic liver glycogen is present as large aggregates in mice, which may contribute to the inflexibility of interconversion between glucose and glycogen in type 2 diabetes, and further that glycogen particles are randomly branched with a size that is related to the rate of glucose release.

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Modeling highly branched structures: Description of the solution structures of dendrimers, polyglycerol, and glycogen

Cited by 7 publications

References 96 publications

Exploring glycogen biosynthesis through Monte Carlo simulation

Exploring glycogen biosynthesis through Monte Carlo simulation

Glycogen as a Building Block for Advanced Biological Materials

Liver glycogen in type 2 diabetic mice is randomly branched as enlarged aggregates with blunted glucose release

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