A good understanding of the mechanism of interaction between inhaled pollutant nanoparticles (NPs) and the pulmonary surfactant monolayer is useful to study the impact of fine particulate matter on human health. In this work, we established coarse-grained models of four representative NPs with different hydrophilicity properties in the air (i.e., CaSO4, C, SiO2, and C6H14O2 NPs) and the pulmonary surfactant monolayer. Molecular dynamic simulations of the interaction during exhalation and inhalation breathing states were performed. The effects of NP hydrophilicity levels, NP structural properties, and cholesterol content in the monolayer on the behaviors of NP embedment or the transmembrane were analyzed by calculating the changes in potential energy, NP displacement, monolayer orderliness, and surface tension. Results showed that NPs can inhibit the ability of the monolayer to adjust surface tension. For all breathing states, the hydrophobic C NP cannot translocate across the monolayer and had the greatest influence on the structural properties of the monolayer, whereas the strongly hydrophilic SiO2 and C6H14O2 NPs can cross the monolayer with little impact. The semi-hydrophilic CaSO4 NP can penetrate the monolayer only during the inhalation breathing state. The hydrophilic flaky NP shows the best penetration ability, followed by the rod-shaped NP and spherical NP in turn. An increase in cholesterol content of the monolayer led to improved orderliness and decreased fluidity of the membrane system due to enhanced intermolecular forces. Consequently, difficulty in crossing the monolayer increased for the NPs.
The structural change of receptor protein at high temperatures is one of the factors affecting the targeting ability of ligand-installed nanocarriers for combined therapy of hyperthermia and drug delivery. In this study, the binding behaviors and mechanisms of integrin αvβ3 receptor and the arginine-glycine-aspartic acid (RGD) peptide ligand at high temperatures were investigated both theoretically and experimentally. The structural parameters of integrin αvβ3 at different temperatures and the interaction forces between the RGD peptide and integrin αvβ3 at different binding sites were calculated by molecular dynamics simulation. Fourier transform infrared spectroscopy, energy dispersive spectroscopy, ultraviolet-visible absorption spectroscopy, and atomic force microscopy were used to analyze the structural changes of integrin αvβ3 and to measure the ligand-receptor interaction. Results show that the number of hydrogen bonds decreased and the secondary structure of integrin αvβ3 changed with the increase in temperature, indicating the denaturation of integrin αvβ3. The structural stability of the integrin αv subunit was better than that of the integrin β3 subunit at high temperatures. The interaction between the RGD peptide and integrin αvβ3 weakened as the temperature increased because the structure of the integrin αvβ3 binding site became more flexible and the corresponding calcium ions were shed from the binding site. The strongest interaction force was exhibited at the binding site of the integrin β3 subunit at 310 K while it was found at the binding site of the integrin αv subunit at higher temperatures, owing to the smaller structure deformation of the integrin αv subunit.integrin αvβ3-RGD peptide, ligand-receptor interaction force, MD simulation and experimental measurement, protein denaturation, temperature-induced Antitumor drug-loaded nanoparticles (NPs) combined with hyperthermia have been widely investigated in tumor treatment. [1][2][3][4][5] In hyperthermia, the morphology of tumor vascular endothelial cells changes and the tumor cell membrane becomes loose, which is beneficial for NPs transporting to the tissue deeply and crossing over the membrane. [6,7] However, the elevated temperature reduces the targeting efficiency of NPs due to receptor denaturation and binding site inactivation. To improve the nano-thermotherapy effect, it is necessary to study the ligand-receptor interaction to gain information about the binding sites that still have binding affinity at high temperatures. [8][9][10] Protein denaturation leads to changes in the binding site structure at high temperatures, and the changes in receptor protein structure with temperature need to be understood to improve the targeted delivery efficiency of NPs. [11][12][13][14] The expression of different proteins on the surface of Hela cells at high temperatures (39-45 C) was
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