Abstract
The cytoskeleton determines cell mechanics and lies at the heart of important cellular functions. Growing evidence suggests that the manifold tasks of the cytoskeleton rely on the interactions between its filamentous components—actin filaments, intermediate filaments, and microtubules. However, the nature of these interactions and their impact on cytoskeletal dynamics are largely unknown. Here, we show in a reconstituted in vitro system that vimentin intermediate filaments stabilize microtubules against depolymerization and support microtubule rescue. To understand these stabilizing effects, we directly measure the interaction forces between individual microtubules and vimentin filaments. Combined with numerical simulations, our observations provide detailed insight into the physical nature of the interactions and how they affect microtubule dynamics. Thus, we describe an additional, direct mechanism by which cells establish the fundamental cross talk of cytoskeletal components alongside linker proteins. Moreover, we suggest a strategy to estimate the binding energy of tubulin dimers within the microtubule lattice.
Highlights
The cytoskeleton determines cell mechanics and lies at the heart of important cellular functions
Our study examined the interactions between microtubules and vimentin intermediate filaments (IFs)
We showed that vimentin IFs stabilize microtubules by direct interactions, which is in strong contrast to previous findings[14], where only interactions between microtubules and short IF peptides were considered
Summary
The cytoskeleton determines cell mechanics and lies at the heart of important cellular functions. Several studies suggest that in cells, microtubules associated with the vimentin IF network are stable: They exhibit increased resistance to drug-induced disassembly[9] and enhanced directional persistence during directed cell migration[18], and they are reinforced against lateral fluctuations[17] Several proteins such as kinesin[8,11], dynein[13,15], plectin[1], and microtubule-actin cross-linking factor (MACF)[10,12] can mediate interactions between IFs and microtubules. In contrast to the cell experiments that showed stabilization of microtubules by IFs, an earlier work found that many IFs, including vimentin, contain tubulin-binding sites and that short peptides containing these binding sites inhibit microtubule polymerization in vitro[14] It is unknown how this effect relates to fully assembled vimentin filaments. This value has previously only been determined by molecular dynamics simulations and kinetic modeling[20,22,27] or by using atomic force microscopy to indent stabilized microtubules[24]
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