Force fluctuations and polymerization dynamics of intracellular microtubules.

Microtubules are highly dynamic biopolymer filaments involved in a wide variety of biological processes including cell division, migration, and intracellular transport. Microtubules are very rigid and form a stiff structural scaffold that resists deformation. However, despite their rigidity, inside of cells they typically exhibit significant bends on all length scales. Here, we investigate the origin of these bends using a Fourier analysis approach to quantify their length and time dependence. We show that, in cultured animal cells, bending is suppressed by the surrounding elastic cytoskeleton, and even large intracellular forces only cause significant bending fluctuations on short length scales. However, these lateral bending fluctuations also naturally cause fluctuations in the orientation of the microtubule tip. During growth, these tip fluctuations lead to microtubule bends that are frozen-in by the surrounding elastic network. This results in a persistent random walk of the microtubule, with a small apparent persistence length of approximately 30 microm, approximately 100 times smaller than that resulting from thermal fluctuations alone. Thus, large nonthermal forces govern the growth of microtubules and can explain the highly curved shapes observed in the microtubule cytoskeleton of living cells.