1.  Cells are not just chemical machines. They pull on their surroundings to move, grow, and decide their fate.

     But most of what we know comes from cells on flat plastic.
     Real tissues are fibrous. 
     So we asked: Do cells follow the same mechanical rules there?

2.  Short answer: No.
     In fibrous environments, cells behave very differently than on flat surfaces. This paper shows why.

3.  On flat surfaces, cells attach mainly at their edges. These attachment points are called focal adhesions.
     That has been the rule for decades.

4.  But in real tissues, cells do not live on flat plates. They sit on fibers, like collagen.

     So we put cells on well-controlled fibrous networks and looked closely.

5.  What we saw was surprising:
     Cells formed strong focal adhesions everywhere, not just at the edges, but also deep inside the cell, far from the periphery.

     So the big question was: How can these interior adhesions even exist?

​

6.  To answer this, we built a mechanical model of the cell. The key insight from the model:
     Fibers allow cells to pull out of the plane, not just sideways. These out-of-plane forces simply do not exist on flat surfaces.

​

7.  The model shows that these 3D forces create local tension hotspots along fibers, even far from the cell edge.

     Where there is tension → adhesions stabilize.

​

8.  Next question: What controls how hard a cell pulls?

     For years, the answer was simple:
     stiffer environment → stronger forces

​

9.  But tissues are not just stiff or soft. They are directional.

     Pulling along fibers ≠ pulling across fibers.

     This creates tension anisotropy (different tension in different directions).

​​

10.  We designed fibrous environments where:

• stiffness increased

• but tension became more evenly distributed

       So stiffness ↑        anisotropy ↓

​

11. What happened?

      Cells pulled less, even though the environment was stiffer.

      This directly contradicts classic mechanobiology.

​​

12. Our theoretical model predicted this. Why?
      Because cells do not respond to stiffness alone, they respond to directional imbalance of tension.

​​

13. When tension is strongly biased in one direction, cells reinforce their contractile machinery.

      When tension becomes more isotropic, that reinforcement weakens, even if stiffness is higher.

​

14. So the model explains a paradox:

      Stiffer environment

      but less directional tension
      leads to weaker cellular forces

      Direction beats magnitude.

.