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Mechanisms of leading edge protrusion in interstitial migration

Research output: Contribution to journalArticle

Kerry Wilson, Alex Lewalle, Marco Fritzsche, Richard Thorogate, Tom Duke, Guillaume Charras

Original languageEnglish
Article number2896
Number of pages12
JournalNature Communications
Volume4
DOIs
StatePublished - 5 Dec 2013

Bibliographical note

© 2013 Macmillan Publishers Limited. All rights reserved. Open Access

King's Authors

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. 

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