Quantitative mapping of cell–cell interactions using the micropipette force sensor

Mechanical interactions among cells play an essential role in immune processes and tumorigenesis. However, quantitative mapping of the interactions between suspended cells remains challenging. In this study, an approach based on micropipette force sensors (MFS) has been developed for accurately manipulating cells and mapping intercellular interactions. The proposed method utilizes a holding probe to support the cells and an MFS probe for interaction force sensing; the intercellular interactions are quantified through force curve measurements in the approach-retraction process. To demonstrate the versatility of our technique, we measured the cell–substrate, cell–adherent, and cell-suspended interactions using mouse neuroblastoma N2a cells (Neuro2A). We demonstrated the potential of our method for measuring various cellular mechanical forces and revealed an increase in the stiffness of Neuro2A cells during mechanical measurements, which may be associated with cytoskeletal reinforcement in response to mechanical stimuli. The proposed technique has substantial implications for studying receptor-ligand effects on immune cells and intercellular adhesion. This advancement provides a method to enhance the comprehension of cellular mechanics and offers a tool for potential biomedical applications.