Biological and Biomimetic Comb Polyelectrolytes

Waigh, Thomas A.; Papagiannopoulos, Aristeidis

doi:10.3390/polym2020057

Cited by 9 publications

(6 citation statements)

References 54 publications

(85 reference statements)

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“…Divalent ions, such as Ca 2+ , are known to reduce swelling in mucin gel networks at low pH, as the acidic groups in the carbohydrate side chains become less charged exposing hydrophobic sites. These hydrophobic interactions form non-covalent cross-links between mucins that lead to and maintain the gel state 5,25,31,54 .…”

Section: Mucin Rheological Behavior and Microstructure As A Function mentioning

confidence: 99%

“…PGM is relatively easy to extract and widely available commercially. In addition, PGM solutions are generally considered a viable system to examine mucus sol-gel behavior due to similarities in physiological function 12,24,25 , although differences between native mucus and PGM solutions were observed in a prior study examining nanoparticle transport 26 . In addition to availability and physiological similarity, another critical benefit in using PGM solutions for fundamental studies is removal of variations in mucin concentration, type, and extraction method, as well as patient to patient variation that occurs with native mucus sources 27,28 .…”

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confidence: 99%

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Chemical and Microstructural Characterization of pH and [Ca2+] Dependent Sol-Gel Transitions in Mucin Biopolymer

Curnutt

Smith

Darrow

et al. 2020

Sci Rep

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Mucus is responsible for controlling transport and barrier function in biological systems, and its properties can be significantly affected by compositional and environmental changes. In this study, the impacts of pH and cacl 2 were examined on the solution-to-gel transition of mucin, the primary structural component of mucus. Microscale structural changes were correlated with macroscale viscoelastic behavior as a function of pH and calcium addition using rheology, dynamic light scattering, zeta potential, surface tension, and ftiR spectroscopic characterization. Mucin solutions transitioned from solution to gel behavior between pH 4-5 and correspondingly displayed a more than tenfold increase in viscoelastic moduli. Addition of CaCl 2 increased the sol-gel transition pH value to ca. 6, with a twofold increase in loss moduli at low frequencies and tenfold increase in storage modulus. changing the ionic conditions-specifically [H + ] and [ca 2+ ]-modulated the sol-gel transition pH, isoelectric point, and viscoelastic properties due to reversible conformational changes with mucin forming a network structure via non-covalent cross-links between mucin chains. Mucin is a polyelectrolyte glycoprotein found in mucus, the structured complex fluid found in all types of organisms from bacteria to humans. In vertebrates, mucus is produced by mucus membranes and can be found lining the eyelids, mouth, and nose, as well as gastrointestinal, respiratory, and genital tracts. Since the 1970s 1 , animal mucus and mucin solutions have been well studied, especially the roles mucus plays in drug delivery 2-6 , disorders like cystic fibrosis 7,8 , and its protective biological functions 9-12. Mucin glycoproteins are present in mucus at concentrations of 1-5%, along with electrolytes (ca. 1%), lipids (1-2%), other proteins (1-2%), and water (90-95%) 13. Despite being present in low concentrations, mucin glycoproteins are primarily responsible for the protective and lubricative functions of mucus within the body. Solubilized mucin behaves as a complex fluid with changing viscoelastic and structural properties in response to its environmental conditions. Mucin glycoproteins are responsible for the majority of the physical properties of mucus, as mucin conformation, intra-and inter-strand bonding, and microstructure changes in response to environmental factors such as pH 6,7,12,14 , temperature 2,15 , and ion content 1,14,16. All these factors affect the reversible supramolecular bonding between functional groups within the protein strands, which modifies the microstructure as well as the mechanical and transport properties of the mucin network. In aqueous solutions, biopolymers like mucin form networks that can change dynamically due to non-covalent crosslinks, including physical entanglements and supramolecular bonding. Mucins resemble a bottle brush polymer with a protein backbone and oligosaccharide (carbohydrate) side chains arranged radially from the backbone. The protein backbone of the mucin biopolymer has areas that are dense w...

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Section: Mucin Rheological Behavior and Microstructure As A Function mentioning

confidence: 99%

mentioning

confidence: 99%

Chemical and Microstructural Characterization of pH and [Ca2+] Dependent Sol-Gel Transitions in Mucin Biopolymer

Curnutt

Smith

Darrow

et al. 2020

Sci Rep

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“…Polymers with comb architectures are one of the most common motifs found naturally as biological viscosity modifiers, and examples include the mucins (all 21 human varieties [313]), aggrecans (in synovial joints and cartilage composites) and versican (an extracellular shock absorber in the brain) [314,315]. Beyond their biological and medical uses, synth etic comb polymer analogues are finding applications in nanotechnology [316].…”

Section: Comb Polymersmentioning

confidence: 99%

Advances in the microrheology of complex fluids

2016

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New developments in the microrheology of complex fluids are considered. Firstly the requirements for a simple modern particle tracking microrheology experiment are introduced, the error analysis methods associated with it and the mathematical techniques required to calculate the linear viscoelasticity. Progress in microrheology instrumentation is then described with respect to detectors, light sources, colloidal probes, magnetic tweezers, optical tweezers, diffusing wave spectroscopy, optical coherence tomography, fluorescence correlation spectroscopy, elastic- and quasi-elastic scattering techniques, 3D tracking, single molecule methods, modern microscopy methods and microfluidics. New theoretical techniques are also reviewed such as Bayesian analysis, oversampling, inversion techniques, alternative statistical tools for tracks (angular correlations, first passage probabilities, the kurtosis, motor protein step segmentation etc), issues in micro/macro rheological agreement and two particle methodologies. Applications where microrheology has begun to make some impact are also considered including semi-flexible polymers, gels, microorganism biofilms, intracellular methods, high frequency viscoelasticity, comb polymers, active motile fluids, blood clots, colloids, granular materials, polymers, liquid crystals and foods. Two large emergent areas of microrheology, non-linear microrheology and surface microrheology are also discussed.

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“…This state is hardly compatible with a simple collapsed random-coil conformation. Mucins, however, have the characteristic features of triblock copolymers with comb glycosylated hydrophilic rigid blocks flanked by flexible globular hydrophobic blocks (Di Cola et al 2008;Waigh and Papagiannopoulos 2010). A characteristic feature of block copolymers is that they can fold to form ordered compact metastable liquid crystalline phases (Halperin 1991).…”

Section: Mucin Polymer Foldingmentioning

confidence: 99%

Supramolecular Dynamics of Mucus

Verdugo

2012

Cold Spring Harbor Perspectives in Medicine

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Our purpose here is not to address specific issues of mucus pathology, but to illustrate how polymer networks theory and its remarkable predictive power can be applied to study the supramolecular dynamics of mucus. Avoiding unnecessary mathematical formalization, in the light of available theory, we focus on the rather slow progress and the still large number of missing gaps in the complex topology and supramolecular dynamics of airway mucus. We start with the limited information on the polymer physics of respiratory mucins to then converge on the supramolecular organization and resulting physical properties of the mucus gel. In each section, we briefly discuss progress on the subject, the uncertainties associated with the established knowledge, and the many riddles that still remain. A ROAD MAPM ucus has a complex set of functions in the airway, including its central role in mucociliary clearance. Defective mucus flow rests at the base of some of the most critical pulmonary pathology, including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma. Research on the intricate mechanisms that regulate mucus rheology, particularly in CF, has been largely focused on mucins and on the defective function of the cystic fibrosis transmembrane conductance regulator (CFTR). The biochemistry and molecular biology of mucins (Perez-Villar and Hill 1999;Chen et al. 2001;Thornton et al. 2008) and the biophysics of the CFTR (Riordan 2005; Sheppard and Welsh 2006) have all received a great deal of attention during this last decade. Even so, the pathophysiology of defective mucus remains largely phenomenological, and an understanding of the mechanisms that make airway mucus transportable is still limited. Mucus is a polymer gel, and this question rests by and large in the domains of the physics and physical chemistry of polymer gels. The matrix of polymer gels forms a supramolecular network with emerging properties that cannot be understood only on the basis of the properties of the molecules that make it. When polymers are constrained to lie close together by physical or chemical bonds, their behavior departs from those of free polymers. A new set of features emerges that is largely determined by polymer-polymer and polymer-solvent interactions, as well as the topological features of the gel's matrix, including the nature and density of interconnections (low/high energy bonds and physical tangles) and the conformational state and mechanical properties of the polymers that make it. Nonetheless, most of the emphasis on mucus research remains focused on the biochemistry and molecular biology of mucins, the giant polymers found in the mucus gel matrix.

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Biological and Biomimetic Comb Polyelectrolytes

Cited by 9 publications

References 54 publications

Chemical and Microstructural Characterization of pH and [Ca2+] Dependent Sol-Gel Transitions in Mucin Biopolymer

Chemical and Microstructural Characterization of pH and [Ca2+] Dependent Sol-Gel Transitions in Mucin Biopolymer

Advances in the microrheology of complex fluids

Supramolecular Dynamics of Mucus

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