Comparative mechanical profiling of MCF-7 cells in 2D and 3D cultures via optical tweezers

Breast cancer cells experience distinct mechanical forces within the 3D tumor microenvironment, and these forces strongly influence cell behavior, invasion potential, and treatment response. While conventional two-dimensional culture systems offer experimental simplicity, they fail to reproduce the complex mechanical interactions present in vivo , which play an important role in the development of therapeutic resistance. In this work, we investigate the mechanical properties of breast cancer cells grown under both 2D and 3D conditions using dual-beam optical tweezers. Our measurements show that cells cultured in 3D exhibit lower deformability compared with cells cultured in 2D, consistent with the increased physical confinement imposed by a physiologically relevant extracellular matrix. These biomechanical differences correlate with cellular plasticity and drug resistance mechanisms previously observed in 3D cultures. The findings emphasize the critical role of mechanical forces in the tumor microenvironment and highlight the limitations of 2D models for studying cancer cell mechanics. Incorporating biomechanical context using 3D culture systems may therefore provide a more accurate understanding of tumor progression and therapeutic responses.