title: Mechanisms of leading edge protrusion in interstitial migration.
abstract: While the molecular and biophysical mechanisms underlying cell protrusion on two-dimensional substrates are well understood, our knowledge of the actin structures driving protrusion in three-dimensional environments is poor, despite relevance to inflammation, development and cancer. Here we report that, 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. This 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 our experimental data, we propose 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.
authors.affiliation: 1] London Centre for Nanotechnology, University College London, 17-19 Gordon Street, London WC1H 0AH, UK [2].
authors.forename: Kerry
authors.initials: K
authors.lastname: Wilson
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lewalle
authors.forename: Marco
authors.initials: M
authors.lastname: Fritzsche
authors.forename: Richard
authors.initials: R
authors.lastname: Thorogate
authors.forename: Tom
authors.initials: T
authors.lastname: Duke
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charras
mesh_terms: D008841:Actin Cytoskeleton; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D036681:Fluorescence Recovery After Photobleaching; D018922:HL-60 Cells / Q000166:cytology*; D006801:Humans; D046210:Microfluidic Analytical Techniques
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins