TY - JOUR
T1 - Cross-linkers at growing microtubule ends generate forces that drive actin transport
AU - Alkemade, Celine
AU - Wierenga, Harmen
AU - Volkov, Vladimir A.
AU - López, Magdalena Preciado
AU - Akhmanova, Anna
AU - ten Wolde, Pieter Rein
AU - Dogterom, Marileen
AU - Koenderink, Gijsje H.
PY - 2022
Y1 - 2022
N2 - The actin and microtubule cytoskeletons form active networks in the cell that can contract and remodel, resulting in vital cellular processes such as cell division and motility. Motor proteins play an important role in generating the forces required for these processes, but more recently the concept of passive cross-linkers being able to generate forces has emerged. So far, these passive cross-linkers have been studied in the context of separate actin and microtubule systems. Here, we show that cross-linkers also allow actin and microtubules to exert forces on each other. More specifically, we study single actin filaments that are cross-linked to growing microtubule ends, using in vitro reconstitution, computer simulations, and a minimal theoretical model. We show that microtubules can transport actin filaments over large (micrometer-range) distances and find that this transport results from two antagonistic forces arising from the binding of cross-linkers to the overlap between the actin and microtubule filaments. The cross-linkers attempt to maximize the overlap between the actin and the tip of the growing microtubules, creating an affinity-driven forward condensation force, and simultaneously create a competing friction force along the microtubule lattice. We predict and verify experimentally how the average transport time depends on the actin filament length and the microtubule growth velocity, confirming the competition between a forward condensation force and a backward friction force. In addition, we theoretically predict and experimentally verify that the condensation force is of the order of 0.1 pN. Thus, our results reveal an active mechanism for local actin remodeling by growing microtubules that relies on passive cross-linkers.
AB - The actin and microtubule cytoskeletons form active networks in the cell that can contract and remodel, resulting in vital cellular processes such as cell division and motility. Motor proteins play an important role in generating the forces required for these processes, but more recently the concept of passive cross-linkers being able to generate forces has emerged. So far, these passive cross-linkers have been studied in the context of separate actin and microtubule systems. Here, we show that cross-linkers also allow actin and microtubules to exert forces on each other. More specifically, we study single actin filaments that are cross-linked to growing microtubule ends, using in vitro reconstitution, computer simulations, and a minimal theoretical model. We show that microtubules can transport actin filaments over large (micrometer-range) distances and find that this transport results from two antagonistic forces arising from the binding of cross-linkers to the overlap between the actin and microtubule filaments. The cross-linkers attempt to maximize the overlap between the actin and the tip of the growing microtubules, creating an affinity-driven forward condensation force, and simultaneously create a competing friction force along the microtubule lattice. We predict and verify experimentally how the average transport time depends on the actin filament length and the microtubule growth velocity, confirming the competition between a forward condensation force and a backward friction force. In addition, we theoretically predict and experimentally verify that the condensation force is of the order of 0.1 pN. Thus, our results reveal an active mechanism for local actin remodeling by growing microtubules that relies on passive cross-linkers.
KW - cell biophysics
KW - crosstalk
KW - cytoskeleton
KW - kinetic Monte Carlo simulations
KW - self-organization
UR - http://www.scopus.com/inward/record.url?scp=85126355442&partnerID=8YFLogxK
U2 - 10.1073/pnas.2112799119
DO - 10.1073/pnas.2112799119
M3 - Article
C2 - 35271394
AN - SCOPUS:85126355442
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 1091-6490
IS - 11
M1 - e2112799119
ER -