Forces drive basement membrane invasion in Caenorhabditis elegans.

Cáceres R, Bojanala N, Kelley LC, Dreier J, Manzi J, Di Federico F, Chi Q, Risler T, Testa I, Sherwood DR, Plastino J

Proc. Natl. Acad. Sci. U.S.A. 115 (45) 11537-11542 [2018-11-06; online 2018-10-22]

During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here, using the developmental event of anchor cell (AC) invasion in Caenorhabditis elegans, we observe that the AC deforms the BM and underlying tissue just before invasion, exerting forces in the tens of nanonewtons range. Deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, whereas formins and cross-linkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking, or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. Overall force production emerges from this study as one of the main tools that invading cells use to promote BM disruption in C. elegans.

Ilaria Testa

SciLifeLab Fellow

PubMed 30348801

DOI 10.1073/pnas.1808760115

Crossref 10.1073/pnas.1808760115

pii: 1808760115
pmc: PMC6233148

Publications 9.5.0