Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

18-POS Board 18 Nuclear and Cellular Softening is Essential for Invasive Cancer Cells to Migrate and Metastasize

Alakesh Das , Sandeep Kumar, Shamik Sen. IIT Bombay, Mumbai, Maharashtra, India.

Cancer cells metastasis is a multistep complicated process in which cellular biophysical modifications plays one of the very crucial role. During mesenchymal to amoeboidal transition cancer cells undergo certain physical deformations which allows them to migrate through dense 3D matrices. However, it is still not clear how cells induce these modifications and what is the molecular mechanism behind this transformations. Here in our work using highly invasive MDA-MB-231 and HT-1080 cells and less invasive MCF-7 cells we have first demonstrated the existence of an integrin-mediated bi-directional crosstak between MMPs and actomyosin contractility. Further, we have shown that GM6001 treatment induces cellular and nuclear softening. To probe the functional relevance of this biophysical alteration we performed sandwich gel 3D invasion assay and observed that GM6001 treated cells were migration as efficiently as untreated cells. However, addition of divalent cations reversed this softening effects and cells were stuck in their migratory tracks. Further using computational approach we provided the conclusion that both cellular and nuclear plasticity is essential for cells to undergo migration through tight and narrow interfaces.

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