Per A. Larsson

Implementation of the CHARMM Force Field in GROMACS : Analysis of Protein Stability Effects from Correction Maps, Virtual Interaction Sites, and Water Models

CHARMM27 is a widespread and popular force field for biomolecular simulation, and several recent algorithms such as implicit solvent models have been developed specifically for it. We have here implemented the CHARMM force field and all necessary extended functional forms in the GROMACS molecular simulation package, to make CHARMM-specific features available and to test them in combination with techniques for extended time steps, to make all major force fields available for comparison studies in GROMACS, and to test various solvent model optimizations, in particular the effect of Lennard-Jones interactions on hydrogens. The implementation has full support both for CHARMM-specific features such as multiple potentials over the same dihedral angle and the grid-based energy correction map on the ϕ, ψ protein backbone dihedrals, as well as all GROMACS features such as virtual hydrogen interaction sites that enable 5 fs time steps. The medium-to-long time effects of both the correction maps and virtual sites have been tested by performing a series of 100 ns simulations using different models for water representation, including comparisons between CHARMM and traditional TIP3P. Including the correction maps improves sampling of near native-state conformations in our systems, and to some extent it is even able to refine distorted protein conformations. Finally, we show that this accuracy is largely maintained with a new implicit solvent implementation that works with virtual interaction sites, which enables performance in excess of 250 ns/day for a 900-atom protein on a quad-core desktop computer.

Ductile All-Cellulose Nanocomposite Films Fabricated from Core–Shell Structured Cellulose Nanofibrils

Cellulosic materials have many desirable properties such as high mechanical strength and low oxygen permeability and will be an important component in a sustainable biomaterial-based society, but unfortunately they often lack the ductility and formability offered by petroleum-based materials. This paper describes the fabrication and characterization of nanocomposite films made of core-shell modified cellulose nanofibrils (CNFs) surrounded by a shell of ductile dialcohol cellulose, created by heterogeneous periodate oxidation followed by borohydride reduction of the native cellulose in the external parts of the individual fibrils. The oxidation with periodate selectively produces dialdehyde cellulose, and the process does not increase the charge density of the material. Yet the modified cellulose fibers could easily be homogenized to CNFs. Prior to film fabrication, the CNF was shown by atomic force microscopy to be 0.5-2 μm long and 4-10 nm wide. The films were fabricated by filtration, and besides uniaxial tensile testing at different relative humidities, they were characterized by scanning electron microscopy and oxygen permeability. The strength-at-break at 23 °C and 50% RH was 175 MPa, and the films could, before rupture, be strained, mainly by plastic deformation, to about 15% and 37% at 50% RH and 90% RH, respectively. This moisture plasticization was further utilized to form a demonstrator consisting of a double-curved structure with a nominal strain of 24% over the curvature. At a relative humidity of 80%, the films still acted as a good oxygen barrier, having an oxygen permeability of 5.5 mL·μL/(m(2)·24 h·kPa). These properties indicate that this new material has a potential for use as a barrier in complex-shaped structures and hence ultimately reduce the need for petroleum-based plastics.

Towards natural-fibre-based thermoplastic films produced by conventional papermaking

Materials based on cellulose are predicted to be of great importance in a sustainable society. However, for materials such as paper to replace materials with a higher ecological footprint, they need to be strong, ductile, provide a gas barrier, and, sometimes, also be transparent. Improved properties, or even novel properties, are also important for use outside the conventional markets. This paper describes how cellulose fibres partly derivatised to dialcohol cellulose can be used to fabricate high-density materials by conventional papermaking techniques that simultaneously display all the above-mentioned features. The materials produced were characterised with respect to X-ray diffraction, dynamic mechanical thermal behaviour, visual appearance, oxygen permeability and tensile properties. The highest degree of modification studied, resulted in a material with thermoplastic features, a tensile strength of 57 MPa, a strain-at-break of 44% and an oxygen permeability at 80% RH of 23 ml μm (m2 kPa 24 h)−1. At a thickness of 125 μm, these films have a total light transmittance of 78% (87% haze). However, by hot pressing the film for 2 min at 150 °C under a pressure of 16 MPa, and thereby increasing the density, the total transmittance increases to 89% (23% haze). The hot pressing can also be used to fuse individual pieces together, which is useful in many modern packaging applications. Altogether, this work shows how chemical modification of cellulose fibres can be used to induce novel properties and improve the range of application, and consequently provide an interesting bio-based material with a good potential to replace less sustainable materials.

Strong, Water-Durable, and Wet-Resilient Cellulose Nanofibril-Stabilized Foams from Oven Drying

Porous materials from cellulose nanofibrils (CNFs) have been prepared using Pickering foams from aqueous dispersions. Stable wet foams were first produced using surface-modified CNFs as stabilizing particles. To better maintain the homogeneous pore structure of the foam after drying, the foams were dried in an oven on a liquid-filled porous ceramic frit. The cell structure was studied by scanning electron microscopy and liquid porosimetry, the mechanical properties were studied by compression testing, and the liquid absorption capacity was determined both with liquid porosimetry and by soaking in water. By controlling the charge density of the CNFs, it was possible to prepare dry foams with different densities, the lowest density being 6 kg m(-3), that is, a porosity of 99.6%. For a foam with a density of 200 kg m(-3), the compressive Youngs modulus was 50 MPa and the energy absorption to 70% strain was 2.3 MJ m(-3). The use of chemically modified CNFs made it possible to prepare cross-linked foams with water-durable and wet-resilient properties. These foams absorbed liquid up to 34 times their own weight and were able to release this liquid under compression and to reabsorb the same amount when the pressure was released.

Contact-active antibacterial aerogels from cellulose nanofibrils.

The use of cellulose aerogels as antibacterial materials has been investigated by applying a contact-active layer-by-layer modification to the aerogel surface. Studying the adsorption of multilayers of polyvinylamine (PVAm) and polyacrylic acid to aerogels comprising crosslinked cellulose nanofibrils and monitoring the subsequent bacterial adhesion revealed that up to 26mgPVAmgaerogel(-1) was adsorbed without noticeably affecting the aerogel structure. The antibacterial effect was tested by measuring the reduction of viable bacteria in solution when the aerogels were present. The results show that >99.9% of the bacteria adhered to the surface of the aerogels. Microscopy further showed adherence of bacteria to the surfaces of the modified aerogels. These results indicate that it is possible to create materials with three-dimensional cellulose structures that adsorb bacteria with very high efficiency utilizing the high specific surface area of the aerogels in combination with their open structure.

Bacterial adhesion to polyvinylamine-modified nanocellulose films

Cellulose nanofibril (CNF) materials have been widely studied in recent years and are suggested for a wide range of applications, e.g., medical and hygiene products. One property not very well studied is the interaction between bacteria and these materials and how this can be controlled. The current work studies how bacteria adhere to different CNF materials modified with polyelectrolyte multilayers. The tested materials were TEMPO-oxidized to have different surface charges, periodate-oxidized to vary the water interaction and hot-pressed to alter the surface structure. Then, multilayers were constructed using polyvinylamine (PVAm) and polyacrylic acid. Both the material surface charge and water interaction affect the amount of polymer adsorbed to the surfaces. Increasing the surface charge decreases the adsorption after the first PVAm layer, possibly due to conformational changes. Periodate-oxidized and crosslinked films have low initial polymer adsorptions; the decreased swelling prevents polymer diffusion into the CNF micropore structure. Microscopic analysis after incubating the samples with bacterial suspensions show that only the materials with the lowest surface charge enable bacteria to adhere to the surface because, when adsorbing up to 5 layers PVAm/PAA, the increased anionic surface charge appears to decrease the net surface charge. Both the amounts of PVAm and PAA influence the net surface charge and thus the bacterial adhesion. The structure generated by the hot-pressing of the films also strongly increases the number of bacteria adhering to the surfaces. These results indicate that the bacterial adhesion to CNF materials can be tailored using polyelectrolyte multilayers on different CNF substrates.

Partitioning into Colloidal Structures of Fasted State Intestinal Fluid Studied by Molecular Dynamics Simulations

We performed molecular dynamics (MD) simulations to obtain insights into the structure and molecular interactions of colloidal structures present in fasted state intestinal fluid. Drug partitioning and interaction were studied with a mixed system of the bile salt taurocholate (TCH) and 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLiPC). Spontaneous aggregation of TCH and DLiPC from unconstrained MD simulations at the united-atom level using the Berger/Gromos54A7 force fields demonstrated that intermolecular hydrogen bonding between TCH molecules was an important factor in determining the overall TCH and DLiPC configuration. In bilayered systems, these intermolecular hydrogen bonds resulted in embedded transmembrane TCH clusters. Free energy simulations using the umbrella sampling technique revealed that the stability of these transmembrane TCH clusters was superior when they consisted of 3 or 4 TCH per bilayer leaflet. All-atom simulations using the Slipids/GAFF force fields showed that the TCH embedded in the bilayer decreased the energy barrier to penetrate the bilayer (ΔGpen) for water, ethanol, and carbamazepine, but not for the more lipophilic felodipine and danazol. This suggests that diffusion of hydrophilic to moderately lipophilic molecules through the bilayer is facilitated by the embedded TCH molecules. However, the effect of embedded TCH on the overall lipid/water partitioning was significant for danazol, indicating that the incorporation of TCH plays a crucial role for the partitioning of lipophilic solutes into e.g. lipidic vesicles existing in fasted state intestinal fluids. To conclude, the MD simulations revealed important intermolecular interactions in lipidic bilayers, both between the bile components themselves and with the drug molecules.

On the origin of sorption hysteresis in cellulosic materials

Moisture sorption and moisture sorption hysteresis of carbohydrates are phenomena which affect the utilisation of products made thereof. Although extensively studied, there is still no consensus regarding the mechanisms behind sorption hysteresis. Attempts have been made to link the behaviour to molecular properties, in particular to softening properties, and the moisture sorption hysteresis has therefore here been investigated by modifying cellulosic fibres to affect their softening properties. The results show that the moisture sorption hysteresis diminishes with decreasing softening temperature, and was even completely absent at the higher degrees of modification. The moisture sorption characteristics also changed from a type II sorption to a more type III sorption behaviour, a feature more prominent the higher the degree of modification and the higher the temperature. For the highest degree of modification studied the sorption characteristics changed from sorbing less water the higher the temperature to sorbing more water with increasing temperature.

Native and functionalized micrometre-sized cellulose capsules prepared by microfluidic flow focusing

Cellulose capsules with average outer and inner radii of approximately 44 μm and 29 μm respectively were prepared from cellulose dissolved in a mixture of lithium chloride and dimethylacetamide using a microfluidic flow focusing device (MFFD). The MFFD had three inlets where octane oil in a cellulose solution in silicone oil was used to produce a double emulsion containing a cellulose capsule. This technique enables the formation of capsules with a narrow size distribution which can be beneficial for drug delivery or controlled release capsules. In this respect, cellulose is a highly interesting material since it is known to cause no autoimmune reactions when used in contact with human tissue. Furthermore, by controlling the chemical properties of the cellulose, it is possible to trigger a swelling of the capsules and consequentially the release of an encapsulated substance, e.g. a model drug, when the capsule becomes exposed to an external stimulus. To demonstrate this, capsules were functionalized by carboxymethylation to be pH-responsive and to expand approximately 10% when subjected to a change in pH from 3 to 10. The diffusion constant of a model drug, a 4 kDa fluorescently labelled dextran, through the native capsule wall was estimated to be 6.5 × 10−14 m2 s−1 by fitting fluorescence intensity data to Ficks second law.

On the relationship between fibre composition and material properties following periodate oxidation and borohydride reduction of lignocellulosic fibres

Periodate oxidation followed by borohydride reduction was performed on four structurally different pulp fibres to clarify the effect of chemical composition on the structural and mechanical properties of sheets made from these fibres. The main purpose was to explore the possibility of extending the use of lignocellulose fibres in novel applications. The degree of oxidation, morphological changes, chemical and physical structure of the fibres, the supramolecular ordering of the cellulose and the mechanical performance of handsheets made from the fibres were studied. The results showed that both periodate oxidation and borohydride reduction are more reactive towards the carbohydrates of the fibres and as a result, there is an improvement in the tensile properties of the sheets. If the carbohydrates of the fibres are only periodate oxidised to produce dialdehydes, inter- and intra-fibre crosslinks can be formed, leading to paper with increase strength and higher stiffness. The borohydride reduction results in fibres and papers with a greater strength and ductility. It was also found that the characteristic ductility of these modified papers, emanating from the dialcohol cellulose produced, is limited with lignin-rich fibres.