Grasso Gianvito, Muscat Stefano, Rebella Martina, Morbiducci Umberto, Audenino Alberto, Danani Andrea, Deriu Marco A
Istituto Dalle Molle di Studi sull'Intelligenza Artificiale (IDSIA), Scuola universitaria professionale della Svizzera italiana (SUPSI), Università della Svizzera Italiana (USI), Centro Galleria 2, Manno CH-6928, Switzerland.
Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, IT-10128 Torino, Italy.
J Biomech. 2018 May 17;73:137-144. doi: 10.1016/j.jbiomech.2018.03.036. Epub 2018 Apr 4.
The efficacy of a pharmaceutical treatment is often countered by the inadequate membrane permeability, that prevents drugs from reaching their specific intracellular targets. Cell penetrating peptides (CPPs) are able to route across cells' membrane various types of cargo, including drugs and nanoparticles. However, CPPs internalization mechanisms are not yet fully understood and depend on a wide variety of aspects. In this contest, the entry of a CPP into the lipid bilayer might induce molecular conformational changes, including marked variations on membrane's mechanical properties. Understanding how the CPP does influence the mechanical properties of cells membrane is crucial to design, engineer and improve new and existing penetrating peptides. Here, all atom Molecular Dynamics (MD) simulations were used to investigate the interaction between different types of CPPs embedded in a lipid bilayer of dioleoyl phosphatidylcholine (DOPC). In a greater detail, we systematically highlighted how CPP properties are responsible for modulating the membrane bending modulus. Our findings highlighted the CPP hydropathy strongly correlated with penetration of water molecules in the lipid bilayer, thus supporting the hypothesis that the amount of water each CPP can route inside the membrane is modulated by the hydrophobic and hydrophilic character of the peptide. Water penetration promoted by CPPs leads to a local decrease of the lipid order, which emerges macroscopically as a reduction of the membrane bending modulus.
药物治疗的疗效常常受到膜通透性不足的阻碍，这使得药物无法到达其特定的细胞内靶点。细胞穿透肽（CPPs）能够将包括药物和纳米颗粒在内的各种类型的货物运输穿过细胞膜。然而，CPPs的内化机制尚未完全了解，并且取决于很多方面。在这种情况下，一种CPP进入脂质双层可能会引起分子构象变化，包括膜力学性质的显著改变。了解CPP如何影响细胞膜的力学性质对于设计、改造和改进新的及现有的穿透肽至关重要。在此，使用全原子分子动力学（MD）模拟来研究嵌入二油酰磷脂酰胆碱（DOPC）脂质双层中的不同类型CPP之间的相互作用。更详细地说，我们系统地强调了CPP的性质如何调节膜弯曲模量。我们的研究结果突出了CPP的亲水性与水分子在脂质双层中的渗透密切相关，从而支持了这样一种假设，即每个CPP能够运输到膜内的水量是由肽的疏水和亲水特性调节的。CPPs促进的水渗透导致脂质有序性的局部降低，这在宏观上表现为膜弯曲模量的降低。
