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We investigated the thermodynamic, structural, and dynamics changes in dendrimer-membrane systems during dendrimer adsorption to biological membrane systems by combining atomistic molecular dynamics simulations with umbrella sampling techniques to understand the atomistic interactions between the dendrimer and biological membranes. An ethylenediamine core polyamidoamine dendrimer (generation 3) with amine terminal groups and both zwitterionic dipalmitoyl-phosphatidyl-choline (DPPC) and anionic palmitoyl-oleoyl-phosphatidyl glycerol (POPG) lipid bilayer membranes were used as the model dendrimer and biological membranes, respectively, in this study. The free energy of the dendrimer adsorption onto two model membranes with different charge states was quantitatively determined. For the zwitterionic DPPC membrane, the dendrimer has a minimum free energy of approximately 50 kcal/mol, which is 15 kcal/mol higher than that observed in previous studies. The dominant contribution to the adsorption potential energy is the van der Waals attraction between the dendrimer and the DPPC membrane. However, the anionic POPG membrane pulls the positively charged dendrimer with an attractive mean force of about 200 pN, finally positioning the dendrimer in the membrane headgroup region. As a result of these strong attractive dendrimer and membrane interactions, the dendrimer structurally undergoes the transition from spherical to a pancake conformation, which slows its lateral mobility, especially in the presence of the POPG membrane. The bilayer lipid membranes are also perturbed by the dendrimer adsorption.

Neurofilaments are essential cytoskeletal filaments that impart mechanical stability to axons. They are mostly assembled from three neurofilament proteins that form the core of the filament and its sidearms. Adjacent neurofilaments interact with each other through their apposing sidearms and attain unique conformations depending on the ionic condition, phosphorylation state, and interfilament separations. To understand the conformational properties of apposing sidearms under various conditions and gain insight into interfilament interactions, we performed Monte Carlo simulations of neurofilament pairs. We employed a sequence-based coarse-grained model of apposing NF sidearms that are end-tethered to cylindrical geometries according to the stoichiometry of the three neurofilament subunits. Monte Carlo simulations were conducted under different conditions such as phosphorylation state, ionic condition, and interfilament separations. Under saltfree conditions, apposing sidearms are found to adopt mutually excluding stretched but bent away conformations that are reminiscent of a repulsive type of interaction. Under physiological conditions, apposing sidearms are found to be in a coiled conformation, suggesting a short-range steric repulsive type of interaction. Increased sidearm mutual interpenetration and a simultaneous decrease in the individual brush heights were observed as the interfilament separation was reduced from 60 to 40 nm. The observed conformations suggest entropic interaction as a likely mechanism for sidearm-mediated interfilament interactions under physiological conditions. Electronic supplementary materialThe online version of this article

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