Аннотация:Molecular dynamics (MD) approach employing an all-atom force field and special procedures was used to model and design nanocontainers for inclusion of biocompounds and delivery through lipid membrane. Carbon nanotubes may serve as non-immunogenic containers of biocompounds and vehicles delivery to the cell membrane. These two properties – inclusion and transportation – are interconnected and establish the main challenge in nanovehicle design. MD simulation of systems containing a carbon nanotube, water, a lipid bilayer, and a molecule to be delivered is a way to explore the problem.
At the outset, dynamics of penetration of a carbon nanotube (13.5 Å in diameter, length 32 Å) through a model membrane (hydrated palmitoyloleoylphosphatidylcholine bilayer) under the action of an external force was studied. The nanotube was oriented along the normal to the membrane plane. The force was evenly applied to the nanotube’s atoms. Resultant pressure was about 7•104 bar (for comparison, detonation pressure of TNT is much higher, namely 2•105 bar). Under such a pressure the nanotube penetrates the phospholipids bilayer for 200 ps and pops out of the bilayer two phospholipid molecules. The performed calculations enable estimation of correspondence of the time scales to the force impacts, which is important while setting up analogous AFM experiments. In this case, the external force corresponds to the pressure of a cantilever with a nanotube attached to its tip.
Further studies concerned absorptive properties of the nanotube. The carbon nanotube revealed a potential for inclusion of rather small molecules such as polypeptides and cholesterol. Incorporation of the peptide was found to be a spontaneous process and considered as a model self-assembly of a nanodevice, further referred to as a nanosyringe. The nanosyringe based on a capped nanotube with a nanoagent capable of ejection of an active molecule (for instance, a peptide) out of the nanotube was modelled in the lipid membrane.
Release of the peptide was performed by expulsing it in various media, including the lipid membrane. A set of swelling model spheres emulated the releasing compound (it is supposed that some external signal such as light is needed for the activation of release). For this purpose a modified variant of steered molecular dynamics (SMD) was developed. The conformational state of the peptide was studied in view of chemical stability of the substance under the shock action. The initial helical conformation deformed most greatly at ejection of the polypeptide into vacuum and least of all – into the membrane. Apparently, the environment plays a deforming and structure-forming role in this process. Conformational changes of the polypetide molecule are reduced with a decrease of the swelling rate.
