How motor forces determine the shapes of microtubules in living cells

微管的热持久长度为几毫米，但在活细胞中，它们经常被观察到在只有几微米的长度尺度上弯曲，这表明大的非热力的作用。大多数微管的实验力测量都是在体外进行的，与体内发生的情况没有直接关系。因此，微管的力平衡仍然不清楚。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。该项目为研究细胞中的力产生提供了一个新的范例，通过在活细胞中使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结果。大多数基本的哺乳动物细胞功能，包括迁移和细胞分裂，都涉及到被称为微管的半柔性生物聚合物产生的力。了解运动蛋白产生的力如何影响细胞中微管的形状和功能，在许多领域都有应用：细胞运输、细胞骨架力学和细胞生物学、纳米生物技术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。数值模型将为细胞骨架力学模拟的长期发展奠定基础。此外，该项目有助于在多样化、多学科的环境中对研究生和本科生进行教育和培训。本项目由物理部生命系统物理学共同资助。

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.