Force Spectroscopy on a Cell Drum: AFM Measurements on the Basolateral Side of Cells via Inverted Cell Cultures

The elasticity of a cell is one of the most critical measures of the difference between cancerous cells and healthy cells: cancer cells tend to be softer than healthy cells, and highly invasive cells tend to be more elastic than less aggressive cells. In this work, we present the novel "bottom-up" cell force spectroscopy method for the biophysical characterization of cancer cells, in which an atomic force microscopy (AFM) tip approach from the backside of a net-shaped culture substrate exposing the basolateral cell membrane drum, and compare it with the conventional "top-down" AFM measurements. We used two different human pancreatic carcinoma cell lines, PaTu8988S and PaTu8988T. Our bottom-up AFM tip approach provided a more statistically synchronized distribution of the measured elastic moduli of the cells, demonstrating its superior applicability for the clinical use of force spectroscopy, which is not attainable with the conventional top-down AFM approach.