Effects of ECM Degradation Rate, Adhesion, and Drag on Cell Migration in 3D [chapter]

H. C. Wong, W. C. Tang
2011 International Federation for Medical and Biological Engineering Proceedings  
Receptors on the cell surface are used to bind to specific proteins in the extracellular matrix (ECM), and intracellular forces generated by the actomyosin can be transferred to these sites of contact. These cell-ECM interactions are important for cancer invasion, cell differentiation, and wound healing. In particular, cancer metastasis is a process that is highly dependent on cell migration through a 3D matrix. Cells secrete enzymes, such as matrix metalloproteinases ( MMPs), in order to
more » ... , in order to degrade some of the proteins in the ECM and migrate through it. Our 3D model of cell migration serves to investigate how the degradation rate of the ECM influences quantities important for cell-ECM interactions and cell motility. In our model, both the cell-ECM traction and the drag force depended on the bound receptor concentration, and timedependent equations were used to model the reaction between the MMPs and the ECM proteins. Simulations were conducted over a range of degradation coefficient (α) values of 0 to 1 nm 2 /s·molec and for drag coefficients of 0.5, 1, and 2 pN·s/μm. Results show that both the cell-ECM traction and the drag force were larger in magnitude at lower values α where the concentrations of the bound receptors were the highest. Though the cell velocity showed a biphasic relationship with respect to α, this relationship became less pronounced for lower values of the drag coefficient where cell-ECM traction became the most important force acting on the cell. The relative contribution of the traction and drag force is important in determining the range of α needed for maximal cell migration speed. Keywords-ECM degradation, cell-ECM interactions, traction, mathematical model, cell migration. 16. DiMilla P, Barbee K, Lauffenburger D (1991) Mathematical model for the effects of adhesion and mechanics on cell migration speed. Biophys J 60(1): 15-37
doi:10.1007/978-3-642-21729-6_109 fatcat:zziudz4ssjfiji2pvzpdr4lxfq