Cell surface engineering for inhibition of breast cancer cell motility through modulation of mechanotransduction and focal adhesion dynamics

Abstract

Metastasis is a leading cause of mortality in breast cancer and is critically influenced by cell-extracellular matrix (ECM) interactions, mechanical forces, and cellular motility. In this study, we present a cell surface engineering approach using tris(2-carboxyethyl)phosphine (TCEP), a biocompatible thiol-modifying agent, to modulate the biomechanical behavior of breast cancer cells. TCEP treatment increased surface thiol availability, enhanced phosphorylation of focal adhesion kinase (FAK), and promoted the elongation of pFAK-positive focal adhesions, along with cytoskeletal remodeling and stronger cell-ECM adhesion. These molecular and structural changes corresponded with significantly reduced migration and invasion of MCF7 and MDA-MB-231 cells. Using traction force microscopy (TFM), we further observed increased intracellular tension and traction stress, providing quantitative insight into how surface modification regulates mechanotransduction. These findings highlight the potential of cell surface thiol engineering to control cancer cell adhesion and motility, providing a platform for future identification of clinically applicable redox-modulating agents.