How motor forces determine the shapes of microtubules in living cells

1236616PI：Ladd微管具有几毫米的热持久性长度，但在活细胞中，它们经常被观察到弯曲的长度尺度只有几微米，这表明巨大的非热力的作用。大多数用微管进行的实验力测量都是在体外进行的，与体内发生的事情没有直接关系。因此，微管力平衡仍不清楚。这个项目的目的是开发和验证一个生物学上相关的模型，用于研究运动蛋白对微管的作用力。该项目通过用激光切断活细胞中的单个微管，并使用微管力学的数值模型来解释测量结果，为研究细胞中的力产生提供了一种新的范式。大多数哺乳动物细胞的基本功能，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量。对马达蛋白产生的力如何影响细胞中微管的形状和功能的理解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。该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，该项目还有助于在不同的、多学科的环境中对研究生和本科生进行教育和培训。

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.