Secreted footprints organize complex cell migration patterns

Eukaryotic cell migration is essential to biological processes like embryonic development, immune response, wound healing, or cancer metastasis. Successful cell migration usually requires adhesion to an extracellular matrix (ECM), a network of multiple components, such as collagen and glycoproteins. Cells can also modify the matrix by depositing new matrix proteins such as fibronectin. Recent experiments with MDCK epithelial cells on 1D fibronectin micropatterned stripes observed that cells move almost persistently in regions they have previously crawled over, but barely advance into unexplored regions, resulting in oscillatory motion of increasing amplitude. These observations suggest that cells leave behind a footprint that facilitates their own or other cells’ passage. Here, we explore through mathematical modeling how footprint secretion affects cell motility patterns. We simulate cell crawling on micropatterns of different geometries with a phase field model. We hypothesize that local contact with the secreted footprint activates Rac1, a polarity protein at the front of the cell, and find that this minimal assumption can recapitulate many of the experimental observations. Depending on the footprint secretion rate and the response to the footprint, cells can display a variety of motility patterns, including self-confined (sub-diffusive), oscillatory, and ballistic (super-diffusive) motion. These types of motility patterns are recapitulated by a 1D toy model that provides a simple expression for the oscillatory amplitudes and predicts the correct relationship between the model parameters and the transition from oscillatory to persistent motion. Our model provides insight into how cells can use their own traces to guide themselves. It also opens the door to a new mechanism of guided migration in which cells do not rely on external signals or contact to follow each other.