Electrostatic Mechanism for Depolymerization-Based Poleward Force Generation at Kinetochores  

作　　者：L. John Gagliardi Daniel H. Shain 

机构地区：[1]Department of Physics, Rutgers The State University of New Jersey, Camden, NJ, USA [2]Department of Biology, Rutgers The State University of New Jersey, Camden, NJ, USA

出　　处：《Open Journal of Biophysics》2019年第3期198-203,共6页生物物理学期刊（英文）

摘　　要：Experiments implicating bound volume positive charge at kinetochores interacting with negative charge at microtubule free ends have prompted our calculation of the force at kinetochores for chromosome poleward motility during mitosis. We present here a corroborating force calculation between positively charged Hec1 tails in kinetochores and negatively charged C-termini at microtubule free ends. Based on experimentally-known charge magnitudes on Hec1 tails and C-termini at microtubule free ends, an ab initio calculation of poleward (tension) force per microtubule that falls within the experimental range is demonstrated. Due to the locations of C-termini charges on concave sides of splaying microtubules, this attractive force between subsets of low curvature splaying microtubule protofilaments C-termini eventually fails for subsets of protofilaments with more pronounced curvature, thus generating poleward force as microtubules depolymerize in a dynamic coupling, as observed experimentally. The mechanism by which kinetochores establish and maintain a dynamic coupling to microtubules for force production during the complex motions of mitosis remains elusive, and force generation at kinetochores has emerged as a signature problem in chromosome motility. In agreement with experiment, two separate calculations show that attractive electrostatic interactions over nanometer distances account for poleward chromosome forces at kinetochores.Experiments implicating bound volume positive charge at kinetochores interacting with negative charge at microtubule free ends have prompted our calculation of the force at kinetochores for chromosome poleward motility during mitosis. We present here a corroborating force calculation between positively charged Hec1 tails in kinetochores and negatively charged C-termini at microtubule free ends. Based on experimentally-known charge magnitudes on Hec1 tails and C-termini at microtubule free ends, an ab initio calculation of poleward (tension) force per microtubule that falls within the experimental range is demonstrated. Due to the locations of C-termini charges on concave sides of splaying microtubules, this attractive force between subsets of low curvature splaying microtubule protofilaments C-termini eventually fails for subsets of protofilaments with more pronounced curvature, thus generating poleward force as microtubules depolymerize in a dynamic coupling, as observed experimentally. The mechanism by which kinetochores establish and maintain a dynamic coupling to microtubules for force production during the complex motions of mitosis remains elusive, and force generation at kinetochores has emerged as a signature problem in chromosome motility. In agreement with experiment, two separate calculations show that attractive electrostatic interactions over nanometer distances account for poleward chromosome forces at kinetochores.

关 键 词：MITOSIS CHROMOSOME MOTILITY Force ELECTROSTATICS 

分 类 号：R73[医药卫生—肿瘤]