How motor forces determine the shapes of microtubules in living cells

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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.