Mechanisms of Cell Migration through Size-Limiting Environments

Cells can migrate through a basement membrane (BM) which is a highly dense network with very small pores. It has been hypothesized that such migration occurs via either protease degradation or force-induced deformation of BM. A recent experiment demonstrated that breast cancer cells without the ability of protease degradation can invade into a very dense network, implying the important role of the mechanical deformation of BM. In this study, using an agent-based computational model, we investigated how a cell can invade into a dense network. We evaluated the extent of invasion with various properties of the cell and the BM. We found that the cell exhibits quite different invasive behaviors depending on conditions. If the BM has high stiffness, the cell deforms the BM slightly and maintains a relatively round cell shape. By contrast, if the BM also has viscoplastic properties, the cell can invade much deeper by forming a narrow space to migrate, resulting in a highly elongated cell shape. These results are similar to recent experimental observations and provide insights into understanding how a cell migrates through size-limiting environments during physiological processes.