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.
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