Why cancer cells change shape and how physics explains it

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1.  Why do cancer cells sometimes spread and invade, but other times clump together and grow as a tumor mass?

     It turns out the answer is surprisingly simple: energy
     Here is the story:

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2.  Cancer cells live in very different environments. Some regions are soft and porous. Others are stiff and dense. 

     We asked a simple question:
     How does the physical environment tell a cancer cell what shape to take?

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3.  In tissues, cancer cells usually adopt one of three shapes:

     Rounded: squeeze through pores
     Elongated: pull on the extracellular matrix and invade
     Clustered: stick together and grow

     But which one do they choose and why?

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4.  Our hypothesis was simple:

     Cells choose the shape that costs them the least total energy. 

     Not genes
     Not chemical signals
     Just basic physics + biology

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5.  For a cell, energy comes from two main sources:

     Cost of pushing and deforming the surrounding matrix
     Benefit of activating its internal motors (actomyosin)

     Cells balance these two.

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6.  In a soft matrix:
     It is easy to push the environment to spread and elongate, which in turn activates strong internal motors.

     As a result, cells prefer to spread and elongate.

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7.  ​In a stiff matrix:

     Pushing the matrix is expensive. Subsequently, cells prefer to cluster instead.

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8.  To test these model predictions, we grew breast cancer cells inside 3D hydrogels with controlled stiffness.

     Same cells
     Same chemistry
     Only the physical properties changed

     And the cells behaved exactly as predicted.

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9.  Over time:
     • Soft matrices → cells spread and elongated
     • Stiff matrices → cells formed tight clusters

     No genetic changes
     No added signals
     Just mechanics

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10.  We even changed the chemical composition of the matrix, but kept its stiffness and pore size the same. Result?
       Cells behaved the same way.

       Physics beat chemistry.

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11.  This explains something fundamental about cancer:

       Soft regions of tumors may promote a mesenchymal model of invasion
       Stiff regions may promote tumor growth

       Tumor heterogeneity = different physical niches = different cell behaviors.

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12.  Cancer cells behave like energy-minimizing systems.