Mechanosensitivity of cancer cells in contact with soft substrates using AFM
Résumé
Cancer cells are usually found to be softer than usual cells, but their stiffness changes when in contact with different environments , i.e. they are mechanosensitive. Usually, they adhere to a substrate by adapting their cytoskeleton, thus affecting their rheological properties. This feature could become an efficient mechanism used by cancer cells when invading the surrounding tissues, i.e. they could remodel their cytoskeleton in order to achieve particular deformations. Here we study how local rheological properties of cancer cells – measured in AFM force modulation mode – are affected by a change of the environment. Cancer cells are plated on functionalized PolyAcrylAmide (PAA) substrates of different elasticities, as well as on an endothelium substrate. The analysis requires to account for thin viscoelastic substrate corrections, so a new three–layer model has been developped. The main results show that cell rheology is locally different (nucleus, perinuclear, edge locations) and changes with invasiveness. A general mechanosensitive trend is found where the cell elastic modulus G 0 N and transition frequency f T increase with substrate elasticity, but this trend fails with a real endothelium substrate. These effects are investigated further during cell transmigration, where the actin cytoskeleton undergoes a reorganization process necessary to push through the endothelial gap, in agreement with local viscoelasticity changes measured with the AFM. Taken altogether, these results introduce a new possible extravasation mechanism.
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