Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Biophys J. 2010 Jul 7;99(1):144-52. doi: 10.1016/j.bpj.2010.03.039.
A metric of nanoparticle toxicity is the passive permeability rate through cellular membranes. To assess the influence of nanoparticle morphology on this process, the permeability of buckyball-sized molecules through a representative lipid bilayer was investigated by molecular-dynamics simulation. When C(60) was compared with a prototypical opened C(60) molecule and a representative combustion-generated particle, C(68)H(29), the calculated free-energy profiles along the permeation coordinate revealed a sizable variation in form and depth. The orientation of the anisotropic molecules was determined by monitoring the principal axis corresponding to the largest moment of inertia, and free rotation was shown to be hindered in the bilayer interior. Diffusion constant values of the permeant molecules were calculated from a statistical average of seven to 10 trajectories at five locations along the permeation coordinate. A relatively minor variation of the values was observed in the bilayer interior; however, local resistance values spanned up to 24 orders of magnitude from the water layer to the bilayer center, due primarily to its exponential dependence on free energy. The permeability coefficient values calculated for the three similarly sized but structurally distinct nanoparticles showed a significant variance. The use of C(60) to represent similarly sized carbonaceous nanoparticles for assessments of toxicity is questioned.
纳米颗粒毒性的度量标准是通过细胞膜的被动渗透率。为了评估纳米颗粒形态对这一过程的影响，通过分子动力学模拟研究了类巴基球大小的分子通过代表性脂质双层的渗透率。当将 C(60)与典型的打开 C(60)分子和代表性燃烧生成的颗粒 C(68)H(29)进行比较时，沿渗透坐标计算出的自由能曲线揭示了形式和深度的显著变化。各向异性分子的取向通过监测对应于最大惯性矩的主轴来确定，并且在双层内部显示出自由旋转受到阻碍。通过在渗透坐标的五个位置处对七个到十个轨迹进行统计平均，计算了渗透分子的扩散常数值。在双层内部观察到值的相对较小变化；然而，由于其对自由能的指数依赖性，局部电阻值在从水层到双层中心的范围内跨越了 24 个数量级。对于三个大小相似但结构不同的纳米颗粒计算出的渗透率系数值显示出显著的差异。质疑使用 C(60)来代表具有相似大小的碳质纳米颗粒进行毒性评估的合理性。
