MULTISCALE MODELING OF NANOPARTICLE TRANSPORT IN CELL MEMBRANE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 纳米颗粒在细胞膜中的转运和相互作用在许多生物医学过程中起着关键作用，例如靶向药物递送和皮肤癌治疗。然而，由于细胞膜的复杂性质和动态运输过程，递送机制仍然没有很好地理解。在建模方面，用分子动力学来模拟纳米颗粒和细胞膜是方便的。然而，MD模拟仅限于几百万个原子，仅代表几纳米的膜尺寸。因此，我们提出了联合收割机的纳米粒子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，通过有限元公式。建议的多尺度建模是一个三层的分层方案，包括（i）纳米粒子和膜的分子模型（ii）原子分子动力学模拟，和（iii）在连续尺度的纳米粒子传输的动力学模型。在所提出的工作中，我们使用分子模拟的纳米粒子的吸收和扩散到细胞膜的分析。所采用的分子建模程序允许（a）阐明双层和纳米颗粒表面之间的相互作用的具体机制，和（B）推导出分子能量和结构参数，用于通过细胞膜扩散的连续模型，从而填补了纳米尺度和宏观尺度之间的现有差距。最后，多尺度建模工具原则上可以定制，以匹配任何不同的纳米颗粒和任何不同的细胞，从而形成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.