Different Mechanical Responses to Substrate Stiffness between Cancer Cells and Normal Cells

Abstract

Metastatic cancer cells persistently interact with tumor microenvironment in every steps of their migrating processes. Understanding the effects of ECM on cancer cells are vital to decipher cancer cell invasion and metastasis. Thousands of molecules in focal adhesions are involved in the force transduction processes. Among them, talin acts as one of the most important participants. Conformational changes of talin caused by force are well researched by using single molecule force microscopies in the last decade. However, correlation between mechanical properties of the cancer cells and forces in focal adhesions in cancer metastasis are not fully understood. Here, we measured the viscoelastic properties of cancer cells on five different substrates and the force on talin in focal adhesions by using custom-made talin tension sensors. In order to find out the working patterns of metastatic cancer cells, we carried out the same measurements in human breast cells (MCF10A), non-invasive human breast cancer cells (MCF-7), and invasive human breast cancer cells (MDA-MB-231). By comparing the results, we found that invasive cancer cells can tune their mechanical properties, both viscoelastic properties and force on talin, accordingly when substrate stiffness are changed. Nonetheless, non-invasive cancer cells and normal cells lack this ability. Furthermore, membrane tether experiments conducted by atomic force microscopy also showed that strength of membrane tethers changed with substrate stiffness in MDA-MB-231 cells, not in MCF10A and MCF7 cells.