Stiff ECM puts the brakes on microtubule growth

Leslie, Mitch

Enclosed in a stiff material, this cell shows numerous slow-growing, long-lasting microtubules (green).

Enclosed in a stiff material, this cell shows numerous slow-growing, long-lasting microtubules (green).
For cells that build new blood vessels, a big life choice is whether to branch. [Related article:] Myers et al. reveal how the extracellular matrix (ECM) influences this decision by altering the cell's microtubule dynamics.

A blood vessel starts to grow when a chain of endothelial cells sets off for a new location. The lead cell guides the others and changes direction by sending out a branch. The researchers previously discovered that whether endothelial cells send out offshoots depends on the stiffness of the ECM—spongy ECM promotes branching. ECM characteristics might affect branching by altering microtubule (MT) dynamics, as MTs are known to influence this process in neurons.

In this study, Myers et al. designed software to track the growth rate and longevity of MTs. Endothelial cells migrating on a stiff surface tended to have slow-growing, long-lasting MTs. By contrast, when the cells sat atop a flexible ECM, MTs grew faster and broke down more often. The researchers found that branching correlated with MT growth rate. Although MT persistence did not correlate with the formation of new branches, it might help existing ones elongate.

Another factor besides stiffness was important. The team's previous study revealed that cells are less likely to branch when they are on a two-dimensional surface than when their surroundings are three-dimensional. Myers et al. found that MTs grew faster in cells in 3D cultures. However, the flexibility of the material no longer affected how long MTs remained intact, suggesting that ECM stiffness modifies only MT growth rate in 3D cultures. The next question to answer, the researchers say, is how the cell translates differences in ECM characteristics into changes in MT dynamics.

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Myers K.A. (2011) J. Cell Biol. 10.1083/jcb.201006009