Microtubule depolymerization induces traction force increase through two distinct pathways

Andrew Rape1, Wei-hui Guo, Yu-li Wang

  • 1Department of Biomedical Engineering, Carnegie Mellon University, 700 Technology Drive, Pittsburgh, PA 15219, USA.

Journal of Cell Science
|December 24, 2011
PubMed

Insights

Microtubule depolymerization increases cell traction forces via two pathways: one myosin II-dependent and FAK-independent, the other FAK-regulated and myosin II-independent, revealing complex force regulation.

Area of Science:

  • Cell Biology
  • Biophysics
  • Mechanobiology

Background:

  • Traction forces are crucial for cell functions.
  • The role of myosin II in microtubule depolymerization-induced force changes is not fully understood.
  • Signaling pathways regulating cellular forces require further elucidation.

Purpose of the Study:

  • To investigate the signaling mechanisms behind increased traction forces after microtubule depolymerization.
  • To determine the dependence of this response on myosin II and focal adhesion kinase (FAK).

Main Methods:

  • Traction force microscopy was employed on cells cultured on micropatterned hydrogels.
  • Nocodazole was used to induce microtubule depolymerization.
  • Pharmacological inhibitors for myosin II and FAK were utilized.

Main Results:

  • Microtubule depolymerization increased traction forces.
  • Inhibition of myosin II did not prevent this force increase.
  • Inhibition of FAK abolished the force increase.
  • The response was independent of FAK in control cells but FAK-dependent when myosin II was inhibited.

Conclusions:

  • Microtubule depolymerization activates distinct, complementary pathways regulating traction forces.
  • A myosin II-dependent, FAK-independent pathway contributes to force regulation.
  • A myosin II-independent, FAK-regulated pathway also enhances traction forces.

Related Concept Videos

Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Anaphase A and B01:39

Anaphase A and B

Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Actin Treadmilling01:18

Actin Treadmilling

Actin filaments undergo polymerization and depolymerization from either end. The polymerization and depolymerization rates depend on the cytosolic concentration of free G-actins. The polymerization rate is generally higher at the plus or barbed end, while the depolymerization rate is higher at the minus or pointed end. At a steady state, critical concentration describes the concentration of free G-actin monomers at which the polymerization rate at the plus end is equal to that of the...
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...