Mechanisms of leading edge protrusion in interstitial migration.-猫眼课题宝

DOI：

10.1038/ncomms3896

发表时间：

2013

期刊：

NATURE COMMUNICATIONS

影响因子：

16.6

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

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

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863902/?report=classic

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. Much of our understanding of the role of actin in cell migration is based on studies of cells moving across two-dimensional surfaces. Wilson et al. show that cells crawling in three dimensions through a narrow channel form two functionally distinct actin networks at the leading edge.