Soft mechano-chemistry of molecular hubs in mitotic spindle: biomechanics and mechanical proofreading at microtubule ends

Abstract

A microtubule (MT) is a long stiff tube-shaped filament formed by a hierarchical organization of a large number of tubulin protein molecules. These filaments constitute a major structural component of the scaffold of a multi-component macromolecular machine called mitotic spindle. The plus ends of the MTs are tethered to some specific binding partners by molecular tethers while those of some others are crosslinked by crosslinking molecules. Because of the non-covalent binding involved in the tethering and crosslinking, the attachments formed are intrinsically 'soft'. These attachments are transient because these can get ruptured spontaneously by thermal fluctuations. By implementing in silico the standard protocols of in vitro molecular force spectroscopy, we compute the lifetimes of simple theoretical models of these attachments. The mean lifetime is essentially a mean first-passage time. The stability of cross-linked antiparallel MTs is shown to decrease monotonically with increasing tension, a characteristic of all 'slip-bonds'. This is in sharp contrast to the nonmonotonic variation of the mean lifetime with tension, a mechanical fingerprint of 'catch-bonds', displayed by the MTs tethered to two distinct binding partners. We mention plausible functional implications of these observations in the context of mechanical proofreading.