Mesh Size Of Network Research Articles

Nanoscale probing and imaging of HIV-1 RNA in cells with a chimeric LNA-DNA sensor.

Real-time detection and nanoscale imaging of human immunodeficiency virus type 1 ribonucleic acid (HIV-1 RNA) in latently infected cells that persist in people living with HIV-1 on antiretroviral therapy in blood and tissue may reveal new insights needed to cure HIV-1 infection. Herein, we develop a strategy combining DNA nanotechnology and super-resolution expansion microscopy (ExM) to detect and image a 22 base sequence transcribed from the HIV-1 promoter in model live and fixed cells. We engineer a chimeric locked nucleic acid (LNA)-DNA sensor via hybridization chain reaction to probe HIV-1 RNA in the U3 region of the HIV-1 long terminal repeat (LTR) by signal amplification in live cells. We find that the viral RNA transcript of the U3 region of the HIV-1 LTR, namely PromA, is a valid and specific biomarker to detect infected live cells. The efficiency and selectivity of the LNA-DNA sensor are evaluated in combination with ExM. Unlike standard ExM methods, which rely on additional custom linkers to anchor and immobilize RNA molecules in the intracellular polymeric network, in the current strategy, we probe and image the HIV-1 RNA target at nanoscale resolution, without resorting to chemical linkers or additional preparation steps. This is achieved by physical entrapment of the HIV-1 viral transcripts in the cells post-expansion by finely tuning the mesh size of the intracellular polymeric network.

Facilitating target search in polymer networks: Effects of target size and mixed one-dimensional and three-dimensional diffusion.

We theoretically investigate the problem of diffusive target search and mean first passage times (MFPTs) of a tracer in a three-dimensional (3D) polymer network with a particular focus on the effects of combined one-dimensional (1D) diffusion along the polymer chains and 3D diffusion within the network. For this, we employ computer simulations as well as limiting theories of a single diffusive tracer searching for a spherical target fixed at a cross-link of a homogeneous 3D cubic lattice network. The free parameters are the target size, the ratio of the 1D and 3D friction constants, and the transition probabilities between bound and unbound states. For a very strongly bound tracer on the chains, the expected predominant set of 1D lattice diffusion (LD) is found. The MFPT in the LD process significantly depends on the target size, yielding two distinct scaling behaviors for target sizes smaller and larger than the network mesh size, respectively. In the limit of a pointlike target, the LD search becomes a random walk process on the lattice, which recovers the analytical solution for the MFPT previously reported by S. Condamin, O. Bénichou, and M. Moreau [Phys. Rev. Lett. 95, 260601 (2005)PRLTAO0031-900710.1103/PhysRevLett.95.260601]. For the very weakly bound tracer, the expected 3D free diffusion (FD) dominates, extrapolating to the well-known Smoluchowski limit. A critical target size is found above which the MFPT in the FD process is faster than in the LD process. For intermediate binding, i.e., a combination of LD and FD processes, the target search time can be minimized for an optimal range of target sizes and partitions between FD and LD, for which the MFPTs are substantially faster when compared to the limiting FD or LD processes. Our study may provide a theoretical basis to better understand and predict search and reaction processes in complex structured materials, thereby contributing to practical applications such as designing nanoreactors where catalytic targets are immobilized in polymer networks.

Kinetics of Network Formation and Heterogeneous Dynamics of an Egg White Gel Revealed by Coherent X-Ray Scattering

The kinetics of heat-induced gelation and the microscopic dynamics of a hen egg white gel are probed using x-ray photon correlation spectroscopy along with ultrasmall-angle x-ray scattering. The kinetics of structural growth reveals a reaction-limited aggregation process with a gel fractal dimension of ≈2 and an average network mesh size of ca. 400nm. The dynamics probed at these length scales reveals an exponential growth of the characteristic relaxation times followed by an intriguing steady state in combination with a compressed exponential correlation function and a temporal heterogeneity. The degree of heterogeneity increases with decreasing length scale. We discuss our results in the broader context of experiments and models describing attractive colloidal gels.

Decoupling diffusion and macromolecular relaxation in the release of vitamin B6 from genipin-crosslinked whey protein networks

This study examined the release of vitamin B6 from a hydrogel made of whey protein isolate (WPI). Work was carried out at ambient temperature without preheating the whey protein. Native-state macromolecules were crosslinked with a nontoxic compound, genipin. Experimentation included a ninhydrin assay with UV–vis absorbance, FTIR, 13C NMR, compression testing, SEM imaging, WPI matrix swelling and vitamin release protocols. It was confirmed that geninin crosslinked effectively the protein chains whose network strength was reinforced with increasing crosslinker concentrations. The modified Flory-Rehner theory predicted the molecular weight between crosslinks, network mesh size and crosslinking density in the swollen WPI gels as a function of added crosslinker. Transport patterns of vitamin B6 through the polymeric matrix were monitored over prolonged periods of observation. These were examined with the generalised Fick’s equation and the Peppas-Sahlin equation to unveil the interplay between diffusion and relaxation dynamics in the anomalous transport of the bioactive compound.

Light Scattering and Rheological Studies of 3D/4D Printable Shape Memory Gels Based on Poly (N,N-Dimethylacrylamide-co-Stearyl Acrylate and/or Lauryl Acrylates).

In this work, we present the structural analysis of 3D/4D printable N,N-dimethylacrylamide (DMAAm)-co-stearyl acrylate (SA) and/or lauryl acrylate (LA)-based shape memory gels (SMGs). We characterized these gels by scanning microscopic light scattering technique (SMILS) where a time- and space-averaged correlation function is obtained to overcome the inhomogeneous media. Thus, the characteristic size of the gel internal network (mesh size, ξ) and crosslinking densities are estimated from the Einstein–Stokes formula. The rheological study of the SMGs revealed information about their mechanical strength and transition temperature. From the experimental storage modulus measured by rheological study, crosslinking density and mesh size of the network were also calculated. Both the techniques suggest that SMG with high crystalline content of SA monomer in the gel network contain smaller mesh size (1.13 nm for SMILS and 9.5 nm for rheology study) and high crosslinking density. The comparative study between the light scattering technique and rheological analysis through the quantitative analysis of crosslinking densities will be important to understand the structural properties of the SMGs.

Tracer Diffusion in Tightly-Meshed Homogeneous Polymer Networks: A Brownian Dynamics Simulation Study.

We report Brownian dynamics simulations of tracer diffusion in regularly crosslinked polymer networks in order to elucidate the transport of a tracer particle in polymer networks. The average mesh size of homogeneous polymer networks is varied by assuming different degrees of crosslinking or swelling, and the size of a tracer particle is comparable to the average mesh size. Simulation results show subdiffusion of a tracer particle at intermediate time scales and normal diffusion at long times. In particular, the duration of subdiffusion is significantly prolonged as the average mesh size decreases with increasing degree of crosslinking, for which long-time diffusion occurs via the hopping processes of a tracer particle after undergoing rattling motions within a cage of the network mesh for an extended period of time. On the other hand, the cage dynamics and hopping process are less pronounced as the mesh size decreases with increasing polymer volume fractions. The interpretation is provided in terms of fluctuations in network mesh size: at higher polymer volume fractions, the network fluctuations are large enough to allow for collective, structural changes of network meshes, so that a tracer particle can escape from the cage, whereas, at lower volume fractions, the fluctuations are so small that a tracer particle remains trapped within the cage for a significant period of time before making infrequent jumps out of the cage. This work suggests that fluctuation in mesh size, as well as average mesh size itself, plays an important role in determining the dynamics of molecules and nanoparticles that are embedded in tightly meshed polymer networks.

Swelling behaviour and glass transition in genipin-crosslinked chitosan systems

High-solid chitosan matrices were prepared to investigate the effect of their swelling on structural relaxation and glass transition. Degree of crosslinking in genipin-crosslinked chitosan networks was measured with a ninhydrin assay and a suitable crosslinker concentration was determined for gels used in swelling and thermomechanical analysis. Fourier transform infrared spectroscopy and wide angle X-ray diffraction examined the intermolecular interactions, crystallinity and amorphicity of the biopolymer networks. Swelling characteristics following immersion in water included approximate equilibrium values of the average molecular weight between crosslinks and network mesh size, e.g. 902 g mol−1 and 110 nm for the preparation with an initial solids content of 60% (w/w) after 80 min of swelling, which were quantified with the modified Flory-Rehner theory. Thermal glass transition temperature was observed in the condensed crosslinked networks (≥ 70% w/w total solids) during differential scanning calorimetry experiments. Time-temperature superposition of rheological measurements, obtained with dynamic oscillation in-shear, generated a master curve describing the viscoelastic behaviour of the system, moving through the rubbery, glass transition region and glassy state. Combined analysis using the modified Arrhenius and William-Landel-Ferry theories determined mechanical glass transition temperatures in the range of −68 to −8 °C for the crosslinked biopolymer at intermediate-solid concentrations (40 to 60% w/w solids). An understanding of the effect of swelling on molecular network characteristics was achieved, which is crucial for greater control in the design of systems for the targeted delivery of bioactive compounds.

The effect of hydrogen bonding on diffusion and permeability in UV-cured Polyacrylate-based networks for controlled release

Polyacrylates are important polymers widely used in pharmaceutical industry such as drug coatings due to their low cost, processability and ease of functionalisation. Chemical functionalities (e.g. H-bonding) can be easily included to modulate the transport of low molecular weight drug-like entities through the network. Understanding how such microscopic structural modifications determine macroscopic diffusion is critical for designing next generation responsive polymers. In this study pulsed field gradient (PFG) 1H NMR measurements of the self-diffusion of a dye molecule (Eosin Y) in a series of polyacrylate networks with differing H-bonding strength were undertaken; it was found that the diffusion of Eosin Y is significantly reduced in networks with H-bonding. Detailed analyses by 1H NMR relaxometry and double quantum (DQ) NMR show that H-bonding can also reduce polymer chain mobility. Furthermore, DSC thermoporometry showed a significant increase in the average network mesh size potentially due to the pre-organization of H-bonding containing monomer during network curing. By introducing the H-bonding disrupter, LiClO4, it was found that the diffusivity of solute becomes positively correlated to the average mesh size across the series of networks. Hence, a modified diffusion model based on hydrodynamic theory is proposed to separate the direct (solute-network) H-bonding contribution to solute diffusion from the indirect contribution arising from monomer pre-ordering induced mesh size reduction. Finally, it is shown that the same direct and indirect contributions to microscopic diffusivity, arising from the H-bond strength of the co-monomers, also contribute significantly to the macroscopic membrane permeability which is similarly subject to H-bond disruption.

Anisotropic Double-Network Hydrogels via Controlled Orientation of a Physical Sacrificial Network

We report a method to create anisotropic double-network (DN) hydrogels, through the controlled orientation of a physical sacrificial network. A cross-linked polyacrylamide hydrogel is synthesized from a solution containing a semirigid anionic polyelectrolyte. Subsequently, the gel is stretched to orient the semirigid polyelectrolyte, which does not relax in the stretched state because of the high contour length in comparison to the mesh size of the polyacrylamide network. The polyelectrolyte is then physically cross-linked with a multivalent cation, ZrCl2O, to fix the anisotropy. Anisotropy was visualized by observing birefringence and quantified by small-angle X-ray scattering. By comparing the scattering in the oriented direction versus perpendicular to the oriented direction, a structural anisotropy factor was calculated. Uniaxial tensile testing was performed on samples of varying prestretch, both parallel and perpendicular to the stretching direction. Young’s modulus, fracture stress, fracture strain, and work of extension were characterized, and the resulting mechanical anisotropy was compared to the structural anisotropy factor. We find that the anisotropy of Young’s modulus and fracture stress is directly controlled by the anisotropy of the sacrificial network, while fracture strain and work of extension show little influence from structural anisotropy. The results of this work demonstrate that prestretching of a physical sacrificial network is a controllable and simple method to create anisotropic DN hydrogels.

Dual-Diffusivity Stochastic Model for Macromolecule Release from a Hydrogel.

A three-dimensional model has been developed to describe the multiphase release of macromolecular drugs encapsulated in a hydrogel. The heterogeneity of network mesh size was considered by assigning varying diffusion coefficients to the network lattices randomly. Using a stochastic approach, the random nature of diffusion of drug molecules was captured within the network. The simplest form of distribution containing two diffusion coefficients was tested. To generate the drug release profiles for experimental validation under the limitation of computational cost, a simple scaling relationship was employed. Unlike the single-diffusivity model, the dual-diffusivity model showed good agreement with the experimental data in describing the release profiles of macromolecular drugs of three different sizes from chemically cross-linked dextran hydrogels.

Surface Response of a Polymer Network: Semi-infinite Network.

We study theoretically the surface response of a semi-infinite viscoelastic polymer network using the two-fluid model. We focus on the overdamped limit and on the effect of the network's intrinsic length scales. We calculate the decay rate of slow surface fluctuations, and the surface displacement in response to a localized force. Deviations from the large-scale continuum response are found at length scales much larger than the network's mesh size. We discuss implications for surface scattering and microrheology. We provide closed-form expressions that can be used for surface microrheology: the extraction of viscoelastic moduli and intrinsic length scales from the motions of tracer particles lying on the surface without doping the bulk material.

Morphology of genipin-crosslinked BSA networks yields a measurable effect on the controlled release of vitamin B6

We examined the morphology of a network made with native BSA molecules being crosslinked with genipin at ambient temperature. Ninhydrin assay, FTIR, WAXD, SEM and mechanical tests documented successful crosslinking that enhanced the structural properties of the three dimensional structure. Its hydrophilic nature allows swelling with water absorption, which can be monitored with the modified Flory-Rehner theory to predict the molecular weight between adjacent crosslinks, network mesh size and crosslinking density as a function of crosslinker addition. Characterisation studies were carried out with a view to developing a delivery vehicle for the controlled release of vitamin B6 over a prolonged period of observation. Moving boundaries associated with swelling of the protein matrix resulted in vitamin transport that could be described with the interplay of diffusional and relaxational kinetics via the Peppas-Sahlin equation. Combination of diffusion and swelling equilibrium theories unveils a measurable effect of network characteristics on vitamin B6 release.

Dynamic Model Metallo‐Supramolecular Dual‐Network Hydrogels with Independently Tunable Network Crosslinks

ABSTRACTHybrid polymer networks emerge between chemical and physical crosslinking, where two different modes of chain connectivity control the material behavior. However, rational relations between their microstructural characteristics, supramolecular kinetics, and the resulting network mechanics and dynamics are not well developed. To address this shortcoming, this study introduces a material platform based on a model dual‐network hydrogel, comprising independently tunable chemical and physical crosslinks. The idea is realized by a click reaction between a tetra‐PEG and a linear‐PEG precursor, whereby the linear block also carries a terpyridine ligand at each end that can form additional physical crosslinks by metal ion–bis(terpyridine) complexation. We change the number of chemical crosslinks by varying the molar mass of the tetra‐PEG, and we independently tune the metallo‐supramolecular bonds by using different metal ions, Mn2+, Zn2+, Co2+, and Ni2+. Based on that modular approach, we study the rheological behavior and the diffusivity of fluorescent polymeric tracers. The dissociation of the metallo‐supramolecular bonds provides a relaxation step, whose timescale and intensity are quantified by a sticky Rouse model. These two characteristics differ not only depending on the metal ion but also according to the chemical network mesh size, which highlights an interplay between the chemical and physical crosslinks. © 2020 The Authors. Journal of Polymer Science Part A: Polymer Chemistry published by Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 330–342

Structure-property relationships of cellulose nanofibril hydro- and aerogels and their building blocks.

As abundant and renewable materials with excellent mechanical and functional properties, cellulose nanomaterials are utilized in advanced structural, optical and electronic applications. However, in order to further improve and develop new cellulose nanomaterials, a better understanding of the interplay between the self-assembled materials and their building blocks is crucial. This paper describes the structure–property relationships between cellulose nanofibrils (CNFs) and their resulting self-assembled structures in the form of hydrogels and aerogels. Rheological experiments revealed that the transition from viscous to elastic state with the corresponding evolution of the properties of the CNF dispersion depends on the aspect ratio and can be described in terms of the dynamic overlap concentration. The elastic shear modulus was dependent on the aspect ratio at very low CNF concentrations, reaching a plateau, where only the concentration of CNFs was relevant. This transition point in shear modulus was exploited to determine the mesh size of the fibril network, which was found to be in excellent agreement with predictions from scaling arguments. These findings highlight the possibility to tune the self-assembled materials response directly from the bottom-up by the CNF particle structure and thus, suggest new assembly routes starting directly from the CNF design.

Effect of network mesh size and swelling to the drug delivery from pH responsive hydrogels

ABSTRACTpH responsive hydrogels are ideal platforms for numerous therapeutic delivery applications, including oral delivery, as they are capable of overcoming the many barriers that must be considered when creating an effective drug delivery system. Understanding of the innate hydrogel network structure and its swelling behavior at environmentally relevant conditions is vital for designing hydrogel network capable of effective controlled drug release. Herein, we explored how to expand traditional techniques of swelling and pore characterization to gain better insight into the performance of anionic microparticles composed of the poly(methyl methacrylate‐co‐acrylic acid) with varying molar percentage of 10, 20, and 30 mol% of MMA, for controlled release of low‐molecular‐weight drugs. By evaluating these carrier systems at environmental conditions, we can observe changes in swelling and pore size of the anionic hydrogel networks as a function of MMA, which was then correlated with the release profiles of the small‐molecular‐weight drug sodium nitrate. With the correlation of the swelling behavior of the networks and the release profiles, we demonstrated how the expansion of swelling parameters at relevant pH values provides further incite for evaluating for the optimal blend for controlled release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48767.

Understanding the effect of freeze-drying on microstructures of starch hydrogels

Freeze-drying treatment results in a marked disordering of starch structures because of the freezing of water and the sublimation of ice crystals. The objective of this work is to evaluate how the freeze-drying affects short-range ordered and crystalline structure, the structural compactness, size of reassemblied aggregates, and mesh size of starch gel network, by use of fourier transform infrared spectroscopy, small angle X-ray scattering and X-ray diffraction. Gels prepared from normal (NMS gel) and high-amylose maize starch (G50 gel) were selected as the model materials. After freeze-drying treatment, the short-range ordered and crystalline structures, the structural compactness, and the mesh size of starch gel network reduced for both starch gels. Long-range periodicity of reassemblied aggregates decreased via thinned amorphous region but unchanged ordered region. Impressively, G50 gel which had more ordered structures and a stronger gel network exhibited a higher resistant ability to the destruction of freeze-drying, and then showed little changes in microstructures after being freeze-dried in comparison with NMS gel. The ordered structures, compact reassemblied aggregates, and high-density mesh size-containing gel network may show a higher resistance to the destruction effect of freeze-drying treatment. This work systematically reveals the structural changes of starch gels subjected to freeze-drying treatment, which provides an in-depth understanding of gels structural changes during processing.

Fatigue-Resistant elastomers

The resistance of a material to the growth of a crack is characterized by fracture toughness under monotonic load, and by fatigue threshold under cyclic load. The fatigue threshold of engineering elastomers is commonly limited to ∼50 J/m2, much below their toughness (103∼105 J/m2). Here we report fatigue-resistant elastomers with threshold beyond 500 J/m2. Such an elastomer is a composite of two elastomers: a lattice of a hard elastomer embedded in a matrix of soft elastomer. Both the hard and soft elastomers are elastically stretchable, with small hysteresis. At a crack front in the composite, the soft matrix shears greatly, which de-concentrates stress in the hard lattice. When the crack advances in the composite, the energy dissipated scales with the feature size of the lattice. By contrast, when a crack advances in a homogeneous elastomer, the energy dissipated scales with the mesh size of the polymer network. The fatigue-resistant elastomers open new opportunities for applications requiring stretchable materials.

Structural relaxation and glass transition in high-solid gelatin systems crosslinked with genipin

Structural relaxation and glass transition were examined in the swelling behaviour of a high-solid biopolymer matrix; genipin-crosslinked gelatin. Degree of swelling was quantified by the Flory-Rehner theory that furnishes estimates of average molecular weight between crosslinks and network mesh size. Fourier transform infrared spectroscopy and wide angle X-ray diffraction described intermolecular interactions and the extent of amorphicity in the crosslinked matrix. Micro differential scanning calorimetry provided evidence of the changing thermodynamic characteristics of the gelatin network in the presence of the crosslinker. Modulated differential scanning calorimetry and small deformation oscillatory rheology unveiled the vitrification properties of the system. Experimental measurements were treated with the time-temperature superposition principle to unveil an extensive master curve through the rubbery, glass transition and glassy states. Viscoelastic behaviour was modelled with the combined predictions of the modified Arrhenius and William-Landel-Ferry theories to pinpoint the mechanical glass transition temperature that was compared with predictions from calorimetry. Comprehensive understanding of polymeric behaviour during swelling affords greater control in the design of targeted delivery matrices for drugs and other bioactive compounds.

Shape Recovery of Spherical Hydrogen-Bonded Multilayer Capsules after Osmotically Induced Deformation.

The mechanical properties of microparticles intended for in vivo applications as drug delivery vehicles are among important parameters that influence their circulation in the blood and govern particle biodistribution. We report on the synthesis of soft but mechanically robust spherical capsules via a hydrogen-bonded multilayer assembly of (poly(N-vinylpyrrolidone), Mw = 10 000 g mol-1) with (poly(methacrylic acid) Mw = 100 000 g mol-1)) (PVPON/PMAA)n in methanol using 4 μm nonporous silica microparticles as sacrificial templates, where n = 5 and 10 and represents the bilayer number. The mechanical properties of (PVPON/PMAA)n spherical capsules were assessed using the osmotic pressure difference method and resulted in an elasticity modulus of 97 ± 8 MPa, which is in the range of Young's modulus for elastomeric networks. We also found that hydrogen-bonded (PVPON/PMAA)10 capsules demonstrated almost complete recovery from a concave buckled inward shape induced by the osmotic pressure difference from the addition of polystyrene sulfonate (PSS) to the capsule solution to their initial spherical shape within 12 h after the PSS solution was rinsed off. The permeability measurements through the capsule shell using fluorescently labeled dextran molecular probes revealed that the average mesh size of the hydrogen-bonded network assembled in methanol is in the range of 3 to 9 nm and is not permeable to FITC-dextran with a molecular weight of >40 000 g mol-1. Our study shows that physically cross-linked polyelectrolyte multilayer capsules are capable of withstanding large deformations, which is essential to the development of adaptable particles for controlled delivery.

Ion transport, polarization and electro-responsive elelctrorheological effect of self-crosslinked poly(ionic liquid)s with different counterions

Self-crosslinked bis(imidazolium)-based poly(ionic liquid)s (PILs) containing different counterions (P[C2DVIM][X], X = BF4−, PF6−, TfO−, TFSI−) are synthesized and the influence of counterions on electro-responsive electrorheological (ER) effect is studied in order to understand the structure-property relationship of crosslinked PIL-based ER system. It is found that the size and type of counterions have a significant influence on ER effect. As the size increases, the ER effect decreases (i.e. BF4− > PF6− > TfO− > TFSI−). Different from the linear PIL-based ER system, however, the P[C2DVIM]X with inorganic counterions shows stronger ER effect compared to P[C2DVIM]X with organic counterions. Meanwhile, the influence of counterions on temperature dependence of ER effect of the crosslinked PIL system is also different from the linear PIL system. By dielectric spectroscopy and X-ray scattering measurements, the mechanism behind the influence is analyzed. It demonstrates that, different from linear PIL system, the ionic aggregation is largely weakened in P[C2DVIM]X and the transport of mobile counterions and interfacial polarization are mainly dominated by the mesh size of crosslinking network. This should be responsible for the different dependence of ER effect on the size and type of counterions between self-crosslinked and linear PIL systems.