We report using molecular dynamics simulations that the shape plays a dominant role in inhaled nanoparticle translocation through the pulmonary surfactant layer.

A growing number of proteins have been identified as knotted in their native structures, with such entangled topological features being expected to play stabilizing roles maintaining both the global fold and the nature of proteins. However, the molecular mechanism underlying the stabilizing effect is ambiguous. Here, we combine unbiased and mechanical atomistic molecular dynamics simulations to investigate how a protein is stabilized by an inherent knot by directly comparing chemical, thermal, and mechanical denaturing properties of two proteins having the same sequence and secondary structures but differing in the presence or absence of an inherent knot. One protein is YbeA from Escherichia coli, containing a deep trefoil knot within the sequence, and the other is the modified protein with the knot of YbeA being removed. Under certain chemical denaturing conditions, the unknotted protein fully unfolds whereas the knotted protein does not, suggesting a higher intrinsic stability for the protein having a knot. Both proteins unfold under enhanced thermal fluctuations but at different rates and with distinct pathways. Opening the hydrophobic core via separation between two a-helices is identified as a crucial step initiating the protein unfolding, which, however, is restrained for the knotted protein by topological and geometrical frustrations. Energy barriers for denaturing the protein are reduced by removing the knot, as evidenced by mechanical unfolding simulations. Finally, yet importantly, no obvious change in size or location of the knot was observed during denaturing processes, indicating that YbeA may remain knotted for a relatively long time during and after denaturation.

As the source of fossil fuels moves toward gas, pipeline flow assurance has attracted considerable efforts in developing gas hydrate inhibitors, especially kinetic inhibitors (KIs), for prevention of gas hydrate formation inside pipelines. Traditional KIs are effective but show poor biodegradability that hinders practical use in specific regions, thus prompting search for new environmentally friendly KIs. Antifreeze proteins (AFPs) that evolved by nature to prevent ice growth are such candidates. However, the distinct differences in the crystal structures of hydrate and ice restrain the capability of AFPs in gas hydrate inhibition. We get inspiration from the type I AFP to design alanine-rich short peptides as a green alternative of KIs. Molecular dynamics simulations reveal the design principle, following which at least two methyl groups with coordinated spatial arrangement dock into neighboring cavities for achieving stable hydrate adsorption, which is key for the hydrate mitigation according to the adsorption–inhibition hypothesis. The mechanism of dual methyl group docking is evidenced by mutation and calculation of work profiles transferring peptides from the hydrate surface to the aqueous solution. By properly introducing lysine into the peptide, interestingly, the hydrate binding and inhibition can be enhanced as the bulky side chain in lysine eases peptide bending that enables more methyl groups docking into hydrate cages. These results can provide useful guidelines for the rational design of green effective hydrate inhibitors.

No abstract

Single-walled carbon nanotubes (SWCNTs) are at present synthesized on a large scale with a variety of applications. The increasing likelihood of exposure to SWCNTs, however, puts human health at a high risk. As the front line of the innate host defense system, the pulmonary surfactant monolayer (PSM) at the air-water interface of the lungs interacts with the inhaled SWCNTs, which in turn inevitably perturb the ultrastructure of the PSM and affect its biophysical functions. Here, using molecular dynamics simulations, we demonstrate how the diameter and length of SWCNTs critically regulate their interactions with the PSM. Compared to their diameters, the inhalation toxicity of SWCNTs was found to be largely affected by their lengths. Short SWCNTs with lengths comparable to the monolayer thickness are found to vertically insert into the PSM with no indication of translocation, possibly leading to accumulation of SWCNTs in the PSM with prolonged retention and increased inflammation potentials. The perturbation also comes from the forming water pores across the PSM. Longer SWCNTs are found to horizontally insert into the PSM during inspiration, and they can be wrapped by the PSM during deep expiration via a tube diameter-dependent self-rotation. The potential toxicity of longer SWCNTs comes from severe lipid depletion and the PSM-rigidifying effect. Our findings could help reveal the inhalation toxicity of SWCNTs, and pave the way for the safe use of SWCNTs as vehicles for pulmonary drug delivery.