MULTISCALE MODELING OF NANOPARTICLE TRANSPORT IN CELL MEMBRANE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 纳米粒子在细胞膜中的传输和相互作用在许多生物医学过程中发挥着关键作用，如靶向给药和皮肤癌治疗。然而，由于细胞膜的复杂性和动态转运过程，其给药机制目前还不是很清楚。在建模方面，采用分子动力学方法可以方便地对纳米粒子和细胞膜进行建模。然而，分子动力学模拟仅限于几百万个原子，仅代表膜大小的几纳米。因此，我们提出将纳米粒子与细胞膜相互作用的分子动力学模拟与细胞膜的粗尺度模型相结合，建立有限元模型。所提出的多尺度模型是一个由(I)纳米颗粒和膜的分子模型(Ii)原子分子动力学模拟和(Iii)纳米颗粒在连续介质尺度上传输的动力学模型组成的三层分层方案。在拟议的工作中，我们使用分子模拟来分析纳米颗粒在细胞膜中的吸收和扩散。所采用的分子模拟程序允许(A)阐明双层和纳米颗粒表面之间相互作用的具体机制，以及(B)推导出在细胞膜扩散的连续介质模型中使用的分子能量和结构参数，从而填补纳米尺度和宏观尺度之间的现有空白。最终，多尺度建模工具原则上可以进行量身定做，以匹配任何不同的纳米颗粒和任何不同的细胞，从而产生一个供公共研究使用的数据库。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Transport and interaction of nanoparticles in cell membranes play a critical role in many biomedical processes such as targeted drug delivery and skin cancer treatment. However, the delivery mechanism is still not well understood due to the complex nature of the cell membrane and dynamic transportation process. In terms of modeling, it is convenient to model the nanoparticles and cell membrane with molecular dynamics. However, MD simulation is limited to a few million atoms representing only a few nm of the membrane size. Thus, we proposed to combine the molecular dynamics simulation of nanoparticles cell membrane interaction together with the coarse scale model of the cell membrane through finite element formulation. The proposed multiscale modeling is a three-tiered hierarchical scheme consists of (i) molecular models of nanoparticles and membrane (ii) atomistic molecular dynamics simulations, and (iii) dynamical models of nanoparticle transport at the continuum scale. In the proposed work, we use molecular simulations for the analysis of nanoparticles absorption and diffusion into cell membrane. The molecular modeling procedures adopted allowed (a) to elucidate the specific mechanisms of interaction between the bi-layer and the nanoparticle surface, and (b) to derive molecular energetic and structural parameters to be employed in the continuum model of diffusion through cell membranes, thus filling the existing gap between the nano-and the macroscale. In the end, the multiscale modeling tool can be tailored in principle to match any different nanoparticle and any different cells, leading to a database for public research use.