Computational insights on the interplay between electrotaxis and mechanotaxis

Understanding how cells migrate in response to external cues has important implications for biology, medicine, and bioengineering. Chemical, mechanical, and electrical signals are the primary drivers of directed cell migration, and each has been extensively studied over the past decades. Among them, chemical cues were the first to be investigated and remain the most widely studied due to their undeniable role in in vivo guidance. Mechanical signals, particularly substrate stiffness gradients, have gained prominence for their ubiquity across cell types and their potential to direct migration. More recently, growing evidence suggests that electrotaxis offers a highly precise and programmable means to guide cell movement. Despite this, these cues are often studied in isolation, whereas in vivo they typically coexist and interact. Using well-established biophysical models, we investigate how mechanical and electrical signals cooperate and how they can be engineered to compete for control over cell migration. Our model shows that an electric field can override and even reverse mechanotaxis. Still, the specific outcomes strongly depend on the cell type or, in other words, on the model parameters that describe how strongly the sensing molecules activate the signaling network. To address this large variability in controlling cell migration, we propose particular steps toward further exploration. To support such future research, we provide a freely available platform for predicting electro-mechanical interactions in cell migration, based on a given cell's sensing and signaling characteristics, which could tailor the mechanical and electrical signals that arise naturally during organ development, cancer invasion, or tissue regeneration.