title: Transient Pinning and Pulling: A Mechanism for Bending Microtubules.
abstract: Microtubules have a persistence length of the order of millimeters in vitro, but inside cells they bend over length scales of microns. It has been proposed that polymerization forces bend microtubules in the vicinity of the cell boundary or other obstacles, yet bends develop even when microtubules are polymerizing freely, unaffected by obstacles and cell boundaries. How these bends are formed remains unclear. By tracking the motions of microtubules marked by photobleaching, we found that in LLC-PK1 epithelial cells local bends develop primarily by plus-end directed transport of portions of the microtubule contour towards stationary locations (termed pinning points) along the length of the microtubule. The pinning points were transient in nature, and their eventual release allowed the bends to relax. The directionality of the transport as well as the overall incidence of local bends decreased when dynein was inhibited, while myosin inhibition had no observable effect. This suggests that dynein generates a tangential force that bends microtubules against stationary pinning points. Simulations of microtubule motion and polymerization accounting for filament mechanics and dynein forces predict the development of bends of size and shape similar to those observed in cells. Furthermore, simulations show that dynein-generated bends at a pinning point near the plus end can cause a persistent rotation of the tip consistent with the observation that bend formation near the tip can change the direction of microtubule growth. Collectively, these results suggest a simple physical mechanism for the bending of growing microtubules by dynein forces accumulating at pinning points.
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL, United States of America.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Kent
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL, United States of America.
authors.forename: Parag S
authors.initials: PS
authors.lastname: Rane
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL, United States of America.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Dickinson
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL, United States of America.
authors.forename: Anthony J C
authors.initials: AJ
authors.lastname: Ladd
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, FL, United States of America.
authors.forename: Tanmay P
authors.initials: TP
authors.lastname: Lele
mesh_terms: D000818:Animals; D001692:Biological Transport; D001696:Biomechanical Phenomena; D002467:Cell Nucleus / Q000378:metabolism; D003198:Computer Simulation; D004398:Dyneins / Q000378:metabolism; D018374:LLC-PK1 Cells; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism; D012399:Rotation; D013552:Swine
chemical_list: D009218:Myosins; D004398:Dyneins