Molecular force spectroscopy of kinetochore-microtubule attachment {\it in silico}: Mechanical signatures of an unusual catch bond and collective effects

TL;DR

This paper uses in silico force spectroscopy models to analyze the mechanical signatures of kinetochore-microtubule attachments, revealing catch-bond behavior and collective effects in multi-microtubule bundles.

Contribution

It introduces a computational model demonstrating catch-bond signatures in kinetochore-microtubule attachments and explores collective effects in multi-microtubule bundles under force.

Findings

Model reproduces catch-bond-like behavior under force-ramp.

Attachment lifetime and rupture force depend nonlinearly on bundle size.

Rebinding effects influence the stability of multi-microtubule attachments.

Abstract

Measurement of the life time of attachments formed by a single microtubule (MT) with a single kinetochore (kt) {\it in-vitro} under force-clamp conditions had earlier revealed a catch-bond-like behavior. In the past the physical origin of this apparently counter-intuitive phenomenon was traced to the nature of the force-dependence of the (de-)polymerization kinetics of the MTs. Here first the same model MT-kt attachment is subjected to external tension that increases linearly with time until rupture occurs. In our {\it force-ramp} experiments {\it in-silico}, the model displays the well known `mechanical signatures' of a catch-bond probed by molecular force spectroscopy. Exploiting this new evidence, we have further strengthened the analogy between MT-kt attachments and common ligand-receptor bonds in spite of the crucial differences in their underlying physical mechanisms. We then extend the formalism to model the stochastic kinetics of an attachment formed by a bundle of multiple parallel microtubules with a single kt considering the effect of rebinding under force-clamp and force-ramp conditions. From numerical studies of the model we predict the trends of variation of the mean life time and mean rupture force with the increasing number of MTs in the bundle. Both the mean life time and the mean rupture force display nontrivial nonlinear dependence on the maximum number of MTs that can attach simultaneously to the same kt.