Models of the Nuclear Pore Biomechanics

核孔生物力学模型

• 批准号: 1728407
• 负责人: Mohammad Mofrad
• 金额: $ 45万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1728407&HistoricalAwards=false
• 关键词: Models; Nuclear; Pore; Biomechanics

Cells in the body use many physical processes to sustain life. Many of them depend on moving large molecules into and out of the nucleus. Such transportation is done through small and complicated pathways, called nuclear pore complexes. Despite the vital importance of the nuclear pore complex in cell biology, little is known about the mechanics and dynamics of the transport of the molecules through them. This project includes fundamental research towards understanding the biomechanics of the nuclear pore complex and transport. Understanding how molecules are actively transported through these pore will ultimately inform creation of new cell-based therapeutic approaches and potentially also create industrial applications of biomimetic artificial pores. This project crosses several disciplinary boundaries including those between biology, chemistry, mechanics, and bioengineering. The multi-disciplinary approach, along with outreach targeted to underrepresented students and student teachers, will help broaden participation of underrepresented groups in research and positively impact science, technology, engineering and mathematics education. The research team will partner with the Berkeley NSF-supported BERET program to introduce the power of computational modeling to high school students.The complex, yet delicate, geometry of the nuclear pore and the fine spatiotemporal resolution at which nucleocytoplasmic transport takes place have hindered the direct, experimental investigations of this mysterious nanopore. Given the limitations of experimental techniques, computational approaches spanning multiple scales can break through to understanding by simulating its activity mechanistically. Computational models offer a strong platform for capturing the nanosecond-scale interactions between transported macromolecular cargos and the nuclear pore at nanometer spatial resolutions to examine the details of nucleocytoplasmic transport phenomena. Using a combination of bioinformatics, computational biology and biophysics modeling approaches, ranging from all-atom molecular dynamics and coarse-grained Brownian dynamics to new agent-based modeling methods, this research will shed light on the structure and function of the nuclear pore complex and the dynamics of nucleocytoplasmic traffic.

身体中的细胞使用许多物理过程来维持生命。 它们中的许多依赖于大分子进出原子核。这种运输是通过小而复杂的途径完成的，称为核孔复合物。尽管核孔复合体在细胞生物学中至关重要，但人们对分子通过它们运输的力学和动力学知之甚少。该项目包括基础研究，以了解核孔复合体和运输的生物力学。了解分子如何通过这些孔主动运输将最终为创建新的基于细胞的治疗方法提供信息，并可能创建仿生人工孔的工业应用。该项目跨越了几个学科的界限，包括生物学，化学，力学和生物工程之间的界限。多学科方法，沿着针对代表性不足的学生和实习教师的外联活动，将有助于扩大代表性不足的群体对研究的参与，并对科学、技术、工程和数学教育产生积极影响。 该研究小组将与伯克利NSF支持的BERET计划合作，向高中生介绍计算建模的力量。核孔复杂而微妙的几何形状和核质运输发生的精细时空分辨率阻碍了对这个神秘纳米孔的直接实验研究。鉴于实验技术的局限性，跨越多尺度的计算方法可以通过模拟其活动机制来突破理解。计算模型提供了一个强有力的平台，用于捕获运输的大分子货物和纳米空间分辨率的核孔之间的纳秒尺度的相互作用，以检查核质运输现象的细节。使用生物信息学，计算生物学和生物物理建模方法的组合，从全原子分子动力学和粗粒度布朗动力学到新的基于代理的建模方法，这项研究将揭示核孔复合物的结构和功能以及核质运输的动态。