Emergent Mitotic Chromosome Motions from a Changing Intracellular pH

L John Gagliardi,Daniel H Shain

doi:10.4236/ojbiphy.2018.81002

Abstract

The mechanism by which chromosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. Equally challenging is an explanation for the timing of poleward, antipoleward, and oscillatory chromosome movements. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation are necessary for chromosome motions. We propose here that the dynamics of mitotic chromosome motions are an emergent property of a changing intracellular pH in combination with electrostatic forces. We explain this mechanism within the context of Complexity Theory, based on the electrostatic properties of tubulin, known cellular electric charge distributions, and the dynamic instability of microtubules.

Highlights

We propose here that the dynamics of mitotic chromosome motions are an emergent property of a changing intracellular pH in combination with electrostatic forces
In the context of complexity theory, we propose that mitotic chromosome motions can be understood as an emergent property of a changing intracellular pH that influences nanoscale electrostatic interactions between 1) microtubules and kinetochores, 2) microtubules and centrosomes, and 3) microtubules and chromosome arms
We propose that a unifying principle can be realized within the framework of complexity theory by attributing the timing of the various post-attachment chromosome motions to pHi-dependent electrostatic interactions between tubulin dimers controlling microtubule disassembly/assembly probability ratios

Summary

Introduction

In the context of complexity theory, we propose that mitotic chromosome motions can be understood as an emergent property of a changing intracellular pH that influences nanoscale electrostatic interactions between 1) microtubules and kinetochores, 2) microtubules and centrosomes, and 3) microtubules and chromosome arms. Given that the electric dipole nature of tubulin dimers likely contributes to the efficiency of aster self-assembly, it follows that microtubule minus ends proximal to centrosomes are positively charged with plus ends negative This assignment of charge signs at microtubule free ends agrees with large-scale computer calculations of the electrostatic properties of microtubules [22]. Measurements have shown that pHi rises to a maximum during prophase and decreases through mitosis This is consistent with the efficient self-assembly of the spindle during prophase, when—due to the higher pHi—the greater expression of negative charge on tubulin dimers (notably C-termini) and centrosomes favors microtubule polymerization and microtubule organizing center nucleation [20] [26]. Subsets of interacting microtubules from opposing half-spindles whose free ends are within critical distances may be composed of both growing and shrinking microtubules, but polymerization probabilities will dominate during prophase due to favorable pHi conditions

Electrostatic Microtubule Disassembly Force at Centrosomes

Electrostatic Microtubule Disassembly Force at Kinetochores

Antipoleward Electrostatic Assembly Force

Complexity Theory Approach to Chromosome Motions

Findings

Conclusions