1️⃣ For years, scientists have known that mechanical tension influences cell behavior. But in our recent study in Nature Materials we found that it is not just the amount of tension—it is the direction!

 

2️⃣ Tension Anisotropy: A New Activation Factor

We found that when fibroblasts experience higher tension in one direction, they activate into highly contractile myofibroblasts.

 

3️⃣ Why Does This Matter?

This transformation is essential for wound healing—but if it goes unchecked, it can lead to excessive scarring and fibrocontractile diseases like fibrosis. Fibrosis not only impairs tissue function but can also promote skin cancer invasion.

 

4️⃣ The Self-Reinforcing Loop:

We saw that fibroblasts extend protrusions that interact with collagen fibers. This sets up a self-reinforcing loop:

💠 Protrusions align collagen fibers

💠 Aligned fibers stabilize and strengthen protrusions

💠 This amplifies tension in one direction

 

5️⃣ Breaking the Loop Stops Activation:

Disrupting this feedback loop—by reducing tension anisotropy or inhibiting protrusions—stopped fibroblasts from activating. This suggests that fibrosis and wound healing could be controlled by tuning stress anisotropy!

 

6️⃣ Tension Anisotropy vs. ECM Stiffness:

Which has a bigger impact on fibroblast activation?

We found that tension anisotropy is more important than ECM stiffness! On soft matrices, anisotropic tension activated fibroblasts more than stiff isotropic environments.

 

7️⃣ Fibroblasts in the Skin: A Natural Example

Why is this exciting?

Because in tissues like skin, fibroblasts experience anisotropic tension due to collagen alignment along Langer’s lines. By modulating tension direction, we may be able to control fibroblast activation!

 

8️⃣ Microtubules: The Missing Piece in Tension Sensing?

When we disrupted microtubules, fibroblasts responded in the opposite way—they activated more under isotropic tension instead of anisotropic tension! This means microtubules are crucial for cells to sense and respond to tension anisotropy

 

9️⃣ Model Prediction:

Our theoretical model predicted and explained fibroblast activation under tension:

When stress was isotropic, fibroblasts stayed inactive.

When stress was anisotropic, activation skyrocketed!

 

🔟 Classical Cell Models Fall Short

However, classical theoretical models failed:

Classical models = stress magnitude matters most

Our model = stress anisotropy is the real driver!

 

1️⃣ 1️⃣ Without Microtubules, Direction Does Not Matter!

With disruption of microtubules, our theoretical model showed that fibroblasts behaved just as classical models predicted—responding only to stress magnitude, not direction!