Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Plasticity of cancer cell migration: Extracellular matrix derives the optimisation of blebbing, adhesions, and spreading.
Melda Tozluoglu

Last modified: 2014-06-09


The molecular requirements and morphology of migrating cells can vary depending on matrix geometry; therefore, predicting the optimal migration strategy or the effect of experimental perturbation is difficult. We present a model of cell motility that encompasses actin polymerisation based protrusions, actomyosin contractility, variable actin-plasma membrane linkage leading to membrane blebbing, cell-extracellular matrix adhesion, and varying extracellular matrix geometries. This is used to explore the theoretical requirements for rapid migration in different matrix geometries. Confined matrix geometries cause profound shifts in the relationship of adhesion and contractility to cell velocity; indeed cell-matrix adhesion is dispensable for migration in discontinuous confined environments. The model is challenged to predict the effect of different combinations of kinase inhibitors and integrin depletion in vivo and in confined matrices based on in vitro 2D measurements. Intravital imaging is used to verify bleb-driven migration at tumour margins, and the predicted response to single and combinatorial manipulations. Further, we investigate the ability of motile cells to adapt changing extracellular matrix geometries, and variable adhesion zones within the cell's path. Here, our model suggests the feedback mechanisms between the forces exerted by cells, and cell-ECM the adhesion strength allows the cells a higher adaptability, at the cost of peak cell velocities.