Probing the importance of ECM alignment on cell migration

Understanding the role our bodies’ tissues play in cell migration is critically important because the basic physiology that allows a cell to migrate along a fibrous extracellular matrix (ECM) is fundamental for human health and goes awry in certain disease states.

Macrophages, for instance, are key cellular mediators of innate immunity that crawl throughout fibrous tissues to detect and eliminate pathogens. Their ability to migrate toward a pathogen is dependent in part on how aligned or disordered the ECM is. Cell migration through ECM is also implicated in cancer metastasis, where fibers within the matrix surrounding a primary tumor become progressively aligned, allowing cells to escape, migrate through blood or lymphatic vessels, and take up residence in vital organs.

One of the key questions behind such a pathophysiology is how the organization or patterning of cell-adhesive ECM ligands influences migration.

In order to test this, Wang et al. developed a new tool to print cell-scale patterns composed of lines of ECM proteins and used this platform to examine the influence of parameters like the size, density and alignment of patterns on cell migration. What they found was that alignment of the ECM pattern was the key factor in dictating a uniaxial, directed cell migration phenotype accompanied with elevated migration speed and efficiency.

They discovered, in fact, that highly aligned focal adhesions correlated with rapid migration over a wide range of ECM patterns, and furthermore, that the alignment of the ECM influenced the localization of Rac1, a key regulator of the protrusive activity required at the front of a migrating cell.

“Now that we have an improved understanding of how ECM ligand distribution affects mesenchymal cell migration from this work, we’ve been working to integrate mechanics and three-dimensionality into our newer models,” said Brendon Baker, an assistant professor at the University of Michigan and one of the paper’s senior authors.

Source: “Extracellular matrix alignment dictates the organization of focal adhesions and directs uniaxial cell migration,” by William Y. Wang, Alexander T. Pearson, Matthew L. Kutys, Colin K. Choi, Michele A. Wozniak, Brendon M. Baker, and Christopher S. Chen, APL Bioengineering (2018). The article can be accessed at https://doi.org/10.1063/1.5052239 .