Dynamic modeling of cancer cell migration in an extracellular matrix fiber network

Abstract

We have established a dynamic modeling framework for predicting spatiotemporal behaviors of cancer cell migration in the extracellular matrix (ECM). Dynamic model of cancer cell migration is integrated from four individual simulations, such as 1) filopodia penetration dynamics into the ECM, 2) intracellular mechanics including remodeling of cellular and nuclear membranes, contractile motion of actin stress fibers, and focal adhesion dynamics, 3) structural mechanics of ECM fiber networks, and 4) reaction diffusion mass transfer of degrading enzymes in the ECM. This work is motivated by experimental observations of malignant cancer cell migration, which shows that abundant filopodial formation in cancer cells is a critical characteristic of aggressive cancer cell which invade into the tissue. The dynamic model presented in this work suggests the mechanical interplay between filopodia of cancer cell and surrounding viscoelastic ECM fiber network. The work presented here compares filopodia dynamics in between soft and stiff ECMs varying its pore size.