Effects of Elasticity and Geometry on Cellular Uptake of Nanoparticles

弹性和几何形状对纳米颗粒细胞摄取的影响PI：高华健，布朗大学摘要本研究的目的是基于皮奥姆？S研究小组开发的一系列理论和模拟技术，研究弹性和几何形状对纳米粒子细胞摄取的影响。拟议的工作将包括发展受体介导的内吞作用的理论模型，计算细胞-颗粒附着的自由能和相图，弹性颗粒与细胞膜的相互作用，大长宽比颗粒的细胞吸收，以及通过非特定和特定相互作用力对接和包裹到细胞膜中的碳纳米管的超大规模粗粒分子动力学模拟。智能优点：拟议的项目补充了布朗大学现有的多学科纳米毒理学实验研究计划，以解决目前对纳米颗粒的弹性和长宽比在细胞吸收碳纳米管和其他潜在有毒纳米颗粒中的作用缺乏了解的问题。拟议的研究将有助于从根本上理解纳米材料进入人类和动物细胞的机制，这是一个关于纳米技术的有益和潜在危险影响的巨大社会关切的问题，预计在未来几十年将生产数千吨纳米材料并将其释放到环境中。该项目还可以为生物医学技术中高效的基因和药物靶向和输送系统的开发提供见解或指导方针。广泛影响：拟议在力学、生物学、生物技术、纳米技术、材料科学、化学和物理等一些传统学术学科之间开展的工作将产生新的知识和基本理解，这可能为纳米和生物技术的广泛应用提供见解和指导方针。拟议研究的教育部分包括培训一名博士生，开发两门生物力学研究生课程，研究经验和对代表不足群体的学生的指导，以及参与到历史上的黑人大学和布朗MRSEC计划中的K-12课程的外联计划。

Effects of elasticity and geometry on cellular uptake of nanoparticlesPI: Huajian Gao, Brown UniversityAbstractThe objective of this proposal is to investigate the effects of elasticity and geometry on cellular uptake of nanoparticles based on a number of theoretical and simulation techniques developed by the PI?s research group on endocytosis and cell mechanics. The proposed work will include development of theoretical models of receptor-mediated endocytosis, calculations of free energy and phase diagrams of cell-particle attachment, interaction between elastic particles and cell membrane, cellular uptake of particles with large aspect ratios, as well as ultra-large scale coarse-grained molecular dynamics simulations of carbon nanotubes docking and wrapping into cell membranes via non-specific and specific interaction forces.Intellectual Merit:The proposed project complements existing multidisciplinary experimental research programs at Brown University on nanotoxicology in addressing the current lack of understanding on the roles of elasticity and aspect ratio of nanoparticles in the cellular uptake of carbon nanotubes and other potentially toxic nanoparticles. The proposed research will contribute to the fundamental understanding of mechanisms by which nanomaterials enter human and animal cells, an issue of tremendous societal concern regarding both beneficial and potential hazardous effects of nanotechnology which are projected to produce and release thousands of tons of nanomaterials into the environment in the coming decades. The project can also provide insights or guidelines for the development of efficient gene and drug targeting and delivery systems in biomedical technology. Broad impact:The proposed work at the interface between a number of traditional academic disciplines including mechanics, biology, biotechnology, nanotechnology, materials science, chemistry and physics will generate new knowledge and fundamental understanding that may provide insights and guidelines for a wide range of applications in nano- and bio-technologies. The educational components of the proposed research include training of a PhD student, development of two graduate courses in biomechanics, research experience and mentoring of students from under-represented groups and participation in the outreach programs to historically black colleges and K-12 in the Brown MRSEC program.