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Combined Single Cell Manipulation and Chemomechanical Modeling to Probe Cell Migration Mechanism during Cell-to-cell Interaction

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Cell motion is a crucial process in a wide variety of biological phenomena, including immune response, wound healing and tumor cell metastasis. While these diverse processes are often driven by chemical signals, environmental mechanical stimulations can also have significant effects. A chemomechanical model to assess the biochemical and biophysical modulators of single cell migration during cell-to-cell interaction can help to understand cell migration in a complex environment that is close to realistic in vivo situation. In this work, we develop a novel chemomechanical model that describes the single cell migration capacity related to concentration gradient of chemoattractant, dynamic adhesion strength and relative motion between cells. Model results show that directed cell migration caused by specific chemokine can be biased by dynamic cell adhesion strength and relative motion between cells. The model is validated by implementing experimental study on single cell migration of leukemia cell on stromal cell layer. Cell adhesions are manipulated with optical tweezers, and time-lapse video is used to record single cell migration with respect to stromal cell retrograde flow. Signaling pathway of CXCR4/SDF1 involved in leukemia cell chemotaixs is discussed to understand the chemomechanical process. Drug AMD3100 is used to block the signaling pathway and cause a result of weakened chemotaxis migration. Experimental results show that the effect of drug treatment varied under different retrograde flow of stromal cell layer, which is in consistent with the theoretical modeling. Our work provides a useful framework to explore essential features of cell migration in complex microenvironments in ways that are much more relevant and consequential for our understanding of cell-to-cell interactions and potential therapeutic strategy.

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