Integration of electrotaxis and durotaxis in cancer cells: Subtle nonlinear responses to electromechanical coupling cues

Cells in living organisms live in multiphysics-coupled environments. There is growing evidence indicating that both exogenous electric field (EEF) and extracellular stiffness gradient (ESG) can regulate directional movement of cells, which are known as electrotaxis and durotaxis, respectively. How single cells respond to the ubiquitous electromechanical coupling cues, however, remains mysterious. Using microfluidic chip-based methodology and finite element-based electromechanical coupling design strategies, we develope an electromechanical coupling microchip system, enabling us to quantitatively investigate polarization and directional migration governed by EEF and ESG at the single cell level. It is revealed that both of electrotaxis and durotaxis nonlinearly depend on the physiological EEF and ESG, respectively. Specific combinations of EEF and ESG can subtly modify the polarization states of single cells and thus induce hyperpolarization and depolarization. Cells can integrate electrotaxis and durotaxis in response to multi-cue microenvironments via subtle mechanisms involving cooperation and competition during cellular electrosensing and mechanosensing. The work offers a platform for quantifying migration and polarization of cells driven by electromechanical cues, which is essential not only for elucidating physiological and pathological processes like embryo development, and invasion and metastasis of cancer cells, but for manipulating cell behaviors in a controllable and programmable fashion.

Automated summary

Cells in living organisms exist in multiphysics-coupled environments, where exogenous electric fields and extracellular stiffness gradients can regulate cell movement and polarization. Research shows that cell responses to these electromechanical cues are nonlinear and can be integrated through cooperation and competition mechanisms. This work provides insights into how cells sense and respond to multiple cues for migration and polarization, with implications for physiological and pathological processes.