Combined Single-Cell Manipulation and Chemomechanical Modeling to Probe Cell Migration Mechanism During Cell-to-Cell...

Spatial presentations of chemical and mechanical information are key parameters for cell migration. However, previous theoretical and experimental studies focus on probing the mechanisms caused by a single type of stimulus, while ignoring the synergetic effects, especially for single cell migration during cell-to-cell interaction. Here we develop a chemomechanical model to assess the biochemical and biophysical modulators of single cell migration during cell-to-cell interaction. This model considers the stimulation of chemoattractant concentration gradient, influence of dynamic adhesion strength and relative motion between cells. The model is validated with single cell manipulation of leukemia cancer cell on stromal cell layer using optical tweezers. Both the modeling and experimental results demonstrate that cell migration velocity caused by chemotaxis can be biased by dynamic adhesion force, which is related to the retrograde flow of stromal cell layer. Besides, the biophysical modulators can influence the effect of drug treatment for specific signaling pathway. Our work provides a quantitative description of single cell migration in a complex environment that is close to realistic in vivo situation and is useful for further exploration of cell signaling pathway during cell-to-cell interactions for investigation of potential therapeutic strategy.