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A tight squeeze: how white blood cells move through small channels.

One of the most remarkable properties of animal cells is their ability to migrate. For experimental convenience, most research to date has concentrated on cell migration on two-dimensional (2D) planar surfaces. Although this has been pivotal to our present understanding of cell migration, many cell types migrate primarily in 3D environments: during development, cells move within the embryo to reach their correct location and, in disease, cancer cells leave the primary tumour to metastasize.

Using microfluidic devices, a team of researchers from the LCN led by Dr Kerry Wilson and Dr Guillaume Charras has now investigated the molecular mechanisms underlying cell movement in confined quasi-3D environments.

In research recently published in Nature Communications, they report that the organisation of the leading edge of migrating cells is radically different in 3D environments than on 2D surfaces. Indeed, during chemotactic migration through microchannels with 5 μm × 5 μm cross-sections, HL60 neutrophil-like cells assemble an actin-rich slab filling the whole channel cross-section at their front rather than a 200nm thin veil of actin as in 2D. The 3D leading edge comprises two distinct F-actin networks: an adherent network that polymerizes perpendicular to cell-wall interfaces and a ‘free’ network that grows from the free membrane at the cell front. Each network is polymerized by a distinct nucleator and, due to their geometrical arrangement, the networks interact mechanically.

On the basis of this experimental data, the team proposes that, during interstitial migration, medial growth of the adherent network compresses the free network preventing its retrograde movement and enabling new polymerization to be converted into forward protrusion.

Dr Guillaume Charras, who headed the research, said: “This discovery underlines the great variety of protrusions that cells use at their front when migrating in 3D environments and will force us to re-examine the biophysical mechanisms that underly cell motility”