How motor forces determine the shapes of microtubules in living cells

运动力如何决定活细胞中微管的形状

• 批准号: 1236616
• 负责人: Anthony Ladd
• 金额: $ 49.9万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1236616&HistoricalAwards=false
• 关键词: How; motor; forces; determine; shapes

1236616PI: LaddMicrotubules have a thermal persistence length of several millimeters but in living cells they are frequently observed to be bent on length scales of just a few microns, indicating the action of large athermal forces. Most experimental force measurements with microtubules have been performed in vitro and are not directly relevant to what happens in vivo. As a result, the microtubule force balance remains unclear. This project aims to develop and validate a biologically relevant model for the forces generated on microtubules by motor proteins. The project offers a new paradigm for investigating force generation in cells, by severing individual microtubules with a laser in living cells, and using numerical models of microtubule mechanics to interpret the measurements. Most essential mammalian cell functions, including migration and cell division, involve force generation by semi-flexible biopolymers called microtubules. An understanding of how the forces generated by motor proteins affect the shapes and thus the function of microtubules in the cell has applications in a number of fields: cellular transport, cytoskeletal mechanics and cell biology, engineering applications in nanobiotechnology and the understanding of diseases such as cancer. The project promotes a collaborative partnership between multiple investigators, involving experiments, modeling and simulations. The numerical model will form the basis for a long-term development of simulations of the mechanics of the cytoskeleton. In addition, the project contributes to the education and training of graduate and undergraduate students in a diverse, multidisciplinary environment.This project is co-funded by the Physics of Living Systems in Physics Division.

1236616PI：Laddmicroutubules的热持久性长度为几毫米，但在活细胞中，经常观察到它们仅在几微米的长度上弯曲，这表明大型运动力的作用。大多数用微管进行了大多数实验力测量，在体外进行了，与体内发生的情况无直接相关。 结果，微管力平衡尚不清楚。该项目旨在开发和验证运动蛋白在微管上产生的力的生物学相关模型。 该项目提供了一种新的范式，用于调查细胞中的力产生，通过在活细胞中用激光切断单个微管，并使用微管力学的数值模型来解释测量值。最重要的哺乳动物细胞功能，包括迁移和细胞分裂，涉及被称为微管的半芬式生物聚合物产生的力。对运动蛋白产生的力如何影响形状的理解，因此微管在细胞中的功能具有许多领域的应用：细胞运输，细胞骨架力学和细胞生物学，工程应用，纳米生物技术中的工程应用以及对癌症等疾病的理解。该项目促进了多个研究人员之间的合作伙伴关系，涉及实验，建模和模拟。数值模型将构成对细胞骨架力学模拟的长期发展的基础。此外，该项目为在多样化的多学科环境中的研究生和本科生的教育和培训做出了贡献。该项目由物理学生物部门的物理系统共同资助。