Electrostatic forces drive poleward chromosome motions at kinetochores

Abstract

BackgroundRecent experiments regarding Ndc80/Hec1 in force generation at kinetochores for chromosome motions have prompted speculation about possible models for interactions between positively charged molecules at kinetochores and negative charge at and near the plus ends of microtubules.DiscussionA clear picture of how kinetochores and centrosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The current paradigm of molecular cell biology requires that specific molecules, or molecular geometries, for force generation be identified. However, it is possible to explain several different mitotic motions—including poleward force production at kinetochores—within a classical electrostatics approach in terms of experimentally known charge distributions, modeled as surface and volume bound charges interacting over nanometer distances.ConclusionWe propose here that implicating Ndc80/Hec1 as a bound volume positive charge distribution in electrostatic generation of poleward force at kinetochores is most consistent with a wide range of experimental observations on mitotic motions, including polar production of poleward force and chromosome congression.

Electrostatic Mechanism for Depolymerization-Based Poleward Force Generation at Kinetochores

“…This essentially proposes that bound, oppositely charged distributions are the underlying cause for poleward chromosome motions. As mentioned above, we recently published a force calculation between Hec1 charges, modeled as an experimentally known bound volume positive charge-"unstructured" positive charge-at kinetochores, and experimentally known negative charge at kinetochore microtubule free plus ends that agrees with experimental measurements of the poleward force for chromosome motility [4]. Here we provide a force calculation between positively charged Hec1 tails in kinetochores and negatively charged C-termini at and near microtubule free ends that confirms our previous proposal.…”

“…A number of currently advanced models involve interactions that are fundamentally electrostatic, including mechanisms for chromosome movements based on protofilament-end splaying. A brief review of current models for force production at kinetochores is given elsewhere [4], where we support the experimental work of Miller et al [3] with an ab initio calculation of the force between bound volume positive charge distributions at kinetochores interacting electrostatically with bound negative charge at free ends of microtubules.…”

“…Consistent with their open structures, a cytosol-saturated kinetochore is expected to have a dielectric constant midway between the kinetochore dry value and cytoplasmic water [16]. Since most condensed-matter (dry) dielectric constants are between 1 and 5, the value for cytoplasmic water dominates, and a conservative midpoint value k = 45 ((80 + 10)/2) will be assumed [4]. Substituting this value in (2), with λ = 29 pC/m, and the distance of the effective charge centers of C-termini charges, r = 3 nm, we have F pf = 0.6n pN/pf (picoNewtons per protofilament).…”

Emergent Mitotic Chromosome Motions from a Changing Intracellular pH

“…review of the voluminous literature on kinetochore force generation as well as an ab initio electrostatics-based calculation of the magnitude of poleward force at kinetochores in support of this model is given elsewhere [39]. Since the numerical details of force production at kinetochores are not required in the present work, it will suffice here to outline the broad features of the calculation.…”

“…As discussed elsewhere, non-penetrating microtubules may also contribute to poleward force production at both centrosomes [34] and kinetochores [39].…”