Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing 100084, PR China.
Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing 100084, PR China.
Biomaterials. 2014 Jul;35(23):6069-77. doi: 10.1016/j.biomaterials.2014.03.087. Epub 2014 Apr 26.
Clarifying the mechanisms of cellular interactions of graphene family nanomaterials is an urgent issue to the development of guidelines for safer biomedical applications and to the evaluation of health and environment impacts. By combining large-scale computer simulations, theoretical analysis, and experimental discussions, here we present a systematic study on the interactions of graphene nanosheets having various oxidization degrees with a model lipid bilayer membrane. In the mesoscopic simulations, we investigate the detailed translocation pathways of these materials across a 56 × 56 nm(2) membrane patch which allows us to fully consider the role of membrane perturbation during this process. A phase diagram regarding the transmembrane translocation mechanisms of graphene nanosheets is thereby obtained in the space of oxidization degree and particle size. Then, we propose a theoretical approach to analyze the effects of various initial equilibrium states of graphene nanosheets with membrane on their following cellular uptake process. Finally, we demonstrate that the simulation and theoretical results reproduce some important experimental findings towards the mechanisms of cytotoxicity and antibacterial activity of graphene materials. These results not only provide new insight into the cellular internalization mechanism of graphene-based nanomaterials but also offer fundamental understanding on their physicochemical properties which can be precisely tailored for safer biomedical and environment applications.
阐明石墨烯家族纳米材料的细胞相互作用机制，对于制定更安全的生物医学应用指南以及评估其对健康和环境的影响，是一个亟待解决的问题。本研究通过结合大规模计算机模拟、理论分析和实验讨论，对具有不同氧化程度的石墨烯纳米片与模型脂质双层膜的相互作用进行了系统研究。在介观模拟中，我们研究了这些材料穿过 56×56nm² 膜片的详细迁移途径，这使我们能够充分考虑到在这个过程中膜扰动的作用。因此，在氧化程度和粒径的空间中，得到了关于石墨烯纳米片跨膜迁移机制的相图。然后，我们提出了一种理论方法来分析石墨烯纳米片与膜的各种初始平衡状态对其后续细胞摄取过程的影响。最后，我们证明了模拟和理论结果再现了一些关于石墨烯材料细胞毒性和抗菌活性机制的重要实验发现。这些结果不仅为基于石墨烯的纳米材料的细胞内化机制提供了新的见解，也为其物理化学性质提供了基本的理解，这些性质可以被精确地调整，以应用于更安全的生物医学和环境领域。
