Background

One of the most remarkable properties of animal cells is their ability to migrate. Most research to date has concentrated on cell migration on two-dimensional planar surfaces. Although this has been crucial to our present understanding of cell migration, many cell types migrate primarily in three-dimensional (3D) environments: during development, cells migrate within the embryo to reach their correct location and, in disease, cancer cells leave the primary tumour to metastasise. Particularly relevant are leukocytes which must be able to migrate in a wide variety of tissues to efficiently carry out their immune function.

Past work

Our lab has been studying the chemotactic migration of neutrophils through small cross-section channels with dimensions similar to the gap diameters they encounter during intravascular crawling, transmigration, and migration through connective tissues. We found that the migrating cells form two distinct actin networks: an inner network that polymerises from the free membrane at the cell front and an outer network that grows perpendicular to cell-wall interfaces. Each network is polymerised by a distinct nucleator and, due to their geometrical arrangement, the networks interact mechanically. Removal of the inner network causes a switch in the protrusions type, but not an inhibition of migration, reemphasising the plasticity of migration in 3D environments.

Currently in the lab

Following on from this work, we are currently examining the interplay between intermediate- and end-stage chemoattractants during guidance of neutrophils using microfluidic devices integrating an endothelial layer cultured on a thick collagen gel. This allows examination of transmigration as well as migration in 3D.

Relevant publications:

[1] Wilson, K., Lewalle, A., Fritzsche, M., Thorogate, R., Duke, T. and Charras, G., 2013. Mechanisms of leading edge protrusion in interstitial migration. Nature communications, 4.

Collaborators on this project:

Aleksandar Ivetic (King’s College London, London, UK)

Funding on this project:

Biotechnology and Biological Sciences Research Council (BBSRC)