Biological membranes form both intra- and intercellular nanotubes that are used for molecular sorting within single cells and for long-distance connections between different cells. Such nanotubes can also develop from synthetic lipid bilayers in their fluid state. Each nanotube has a large area-to-volume ratio and stably encloses a water channel that is thereby shielded from its surroundings. The tubes are rather flexible and can easily change both their length and their conformation. Here, we study nanotubes formed by liquid-ordered (Lo) and liquid-disordered (Ld) membranes with three lipid components exposed to aqueous mixtures of two polymers, polyethylene glycol (PEG) and dextran. Both types of membranes form striking patterns of nanotubes when we reduce the volume of giant vesicles by osmotic deflation, thereby exposing the two bilayer leaflets of the membranes to polymer solutions of different composition. With decreasing volume, three different patterns are observed corresponding to three distinct vesicle morphologies that reflect the interplay of spontaneous curvature and aqueous phase separation. We show that tube nucleation and growth is governed by two kinetic pathways and that the tubes undergo a novel shape transformation from necklace-like to cylindrical tubes at a certain critical tube length. We deduce the spontaneous curvature generated by the membrane-polymer interactions from the observed vesicle morphologies using three different and independent methods of image analysis. The spontaneous curvature of the Ld membranes is found to be 4.7 times larger than that of the Lo membranes. We also show that these curvatures are generated by weak PEG adsorption onto the membranes, with a binding affinity of about 1.6 kBT per chain. In this way, our study provides a direct connection between nanoscopic membrane shapes and molecular interactions. Our approach is rather general and can be applied to many other systems of interest such as polymersomes or membrane-bound proteins and peptides.

Fusion of bilayer membranes is studied via dissipative particle dynamics (DPD) simulations. A new set of DPD parameters is introduced which leads to an energy barrier for flips of lipid molecules between adhering membranes. A large number of fusion events is monitored for a vesicle in contact with a planar membrane. Several time scales of the fusion process are found to depend exponentially on the membrane tension. This implies an energy barrier of about 10k(B)T for intermembrane flips and a second size-dependent barrier for the nucleation of a small hemifused membrane patch.

The fusion of lipid bilayers is studied with dissipative particle dynamics simulations. First, to achieve control over membrane properties, the effects of individual simulation parameters are studied and optimized. Then, a large number of fusion events for a vesicle and a planar bilayer are simulated using the optimized parameter set. In the observed fusion pathway, configurations of individual lipids play an important role. Fusion starts with individual lipids assuming a splayed tail configuration with one tail inserted in each membrane. To determine the corresponding energy barrier, we measure the average work for interbilayer flips of a lipid tail, i.e., the average work to displace one lipid tail from one bilayer to the other. This energy barrier is found to depend strongly on a certain dissipative particle dynamics parameter, and, thus, can be adjusted in the simulations. Overall, three subprocesses have been identified in the fusion pathway. Their energy barriers are estimated to lie in the range 8-15 k(B)T. The fusion probability is found to possess a maximum at intermediate tension values. As one decreases the tension, the fusion probability seems to vanish before the tensionless membrane state is attained. This would imply that the tension has to exceed a certain threshold value to induce fusion.

Coarse-grained (CG) models of large biomolecular complexes enable simulations of these systems over long timescales that are not accessible for atomistic molecular dynamics (MD) simulations. A systematic methodology, called essential dynamics coarse-graining (ED-CG), has been developed for defining coarse-grained sites in a large biomolecule. The method variationally determines the CG sites so that key dynamic domains in the protein are preserved in the CG representation. The original ED-CG method relies on a principal component analysis (PCA) of a MD trajectory. However, for many large proteins and multi-protein complexes such an analysis may not converge or even be possible. This work develops a new ED-CG scheme using an elastic network model (ENM) of the protein structure. In this procedure, the low-frequency normal modes obtained by ENM are used to define dynamic domains and to define the CG representation accordingly. The method is then applied to several proteins, such as the HIV-1 CA protein dimer, ATP-bound G-actin, and the Arp2/3 complex. Numerical results show that ED-CG with ENM (ENM-ED-CG) is much faster than ED-CG with PCA because no MD is necessary. The ENM-ED-CG models also capture functional essential dynamics of the proteins almost as well as those using full MD with PCA. Therefore, the ENM-ED-CG method may be better suited to coarse-grain a very large biomolecule or biomolecular complex that is too computationally expensive to be simulated by conventional MD, or when a high resolution atomic structure is not even available.

A dense hydrogen‐bond network is responsible for the mechanical and structural properties of polysaccharides. Random derivatization alters the properties of the bulk material by disrupting the hydrogen bonds, but obstructs detailed structure–function correlations. We have prepared well‐defined unnatural oligosaccharides including methylated, deoxygenated, deoxyfluorinated, as well as carboxymethylated cellulose and chitin analogues with full control over the degree and pattern of substitution. Molecular dynamics simulations and crystallographic analysis show how distinct hydrogen‐bond modifications drastically affect the solubility, aggregation behavior, and crystallinity of carbohydrate materials. This systematic approach to establishing detailed structure–property correlations will guide the synthesis of novel, tailor‐made carbohydrate materials.

Differences in the chemical potential of water and the resulting osmotic pressure across semipermeable membranes are of fundamental importance for many biological systems. Here, we calculate the osmotic pressure and the chemical potential of water for polysaccharide solutions by molecular simulations. We set up a method to measure the osmotic pressure in polysaccharide systems at different concentrations and found that for monomers the experimental trend with respect to the solute concentration is reproduced correctly. However, the calculated osmotic pressure values are systematically too low, and two common carbohydrate force fields (FFs) cannot correctly describe the relationship between the osmotic pressure and the degree of polymerization. Therefore, we reparametrized parts of the GLYCAM06 TIP5P FF based on osmotic pressure data. The predictive power of the resulting GLYCAM06 OSMOr14 TIP5P FF is demonstrated for two different sugar molecules over a wide range of concentrations, and additional evaluations for other solution properties show improved agreement with experimental data. Finally, we discuss different methods to obtain the chemical potential of water in solutions.

The complex polymerization dynamics of the microtubule (MT) plus end are closely linked to the hydrolysis of the GTP nucleotide bound to the β-tubulin. The destabilization is thought to be associated with the conformational change of the tubulin dimers from the straight conformation in the MT lattice to a curved conformation. It remains under debate whether this transformation is directly related to the nucleotide state, or a consequence of the longitudinal or lateral contacts in the MT lattice. Here, we present large-scale atomistic simulations of short tubulin protofilaments with both nucleotide states, starting from both extreme conformations. Our simulations indicate that both interdimer and intradimer contacts in both GDP and GTP-bound tubulin dimers and protofilaments in solution bend. There are no observable differences between the mesoscopic properties of the contacts in GTP and GDP-bound tubulin or the intradime and interdimer interfaces.

Hemicellulose polysaccharides play an important role in the swelling behavior of the primary plant cell wall, and molecular dynamics simulations provide the means of gaining a concise understanding of the interactions of hemicellulose polysaccharides with water. Here, we compare four of the main polysaccharide force fields (CHARMM36 TIP3P, GROMOS56A6(CARBO) SPC, GLYCAM06h TIP3P, and GLYCAM06h TIP5P) for the most abundant hemicellulose backbone components. In particular, we compare aggregation, diffusion coefficients, system density, and investigate the free energy of hydration of saccharides in water. We find that the saccharides show nonphysical aggregation at low concentrations with the GLYCAM06h TIP3P force field, which can be rectified by the use of the TIP5P water model. As a result of the aggregation, GLYCAM06h TIP3P does not lead to reasonable diffusion coefficients whereas the diffusion coefficients, as well as the system density, agrees best with experimental data for the GLYCAM06h TIP5P force field. Overall, GLYCAM06h TIP5P gives good agreement with experimental free energy of hydration data for small saccharides. In addition, the free energy of hydration for short polysaccharides calculated with the GLYCAM06h TIP5P force field is consistent with the radial distribution functions between the polysaccharides and water, the hydration number of the polysaccharides, and the hydrogen bonds formed in the system.