Vimentin Intermediate Filaments Stabilize Dynamic Microtubules by Direct Interactions

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, known as 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

Multiscale mechanics and temporal evolution of vimentin intermediate filament networks

“…(4)) that depends on the respective activation energies, E Ab or E Au , and the thermal energy k B T , and a force-dependent term that depends on k B T , the applied force, and the distance of the respective state to the transition state, x b or x u , seeFig. 3c[30]. The sum x c = x b + x u is constant due to detailed balance[31].…”

“…3b), and for pairs of x u and r e,u , by simulating 1000 F (t) curves. Equivalent results are achieved by numerical solutions, as discussed in detail in Ref [30]…”

“…Equivalent results are achieved by numerical solutions, as discussed in detail in Ref. [30]. The distance of the transition state to the bound state, x u , enters r u (Eq.…”

Desmin intermediate filaments and tubulin detyrosination stabilize growing microtubules in the cardiomyocyte

“…What is the mechanism of desmin-dependent stabilization? A recent elegant in vitro study using reconstituted vimentin intermediate filaments and microtubules indicates that intermediate filaments are sufficient to stabilize growing microtubules through electrostatic and hydrophobic interactions 13 . The interaction with intermediate filaments reduces catastrophes and promotes rescues, in strong accordance with our in cellulo findings here.…”

“…Detyrosination promotes microtubule interaction with intermediate filaments 7,12 , and in the absence of desmin, microtubules are disorganized and detyrosination no longer alters myocyte mechanics 7 . Additionally, a recent pre-print indicates that intermediate filaments can directly stabilize dynamic microtubules in vitro 13 . Despite this evidence, the effects of desmin or detyrosination on the dynamics of cardiomyocyte microtubules have not been investigated.…”