1. Forces drive basement membrane invasion in Caenorhabditis elegans
- Author
-
Laura C. Kelley, Qiuyi Chi, David R. Sherwood, Thomas Risler, Nagagireesh Bojanala, Ilaria Testa, Julie Plastino, Fahima Di Federico, John Manzi, Rodrigo Cáceres, Jes Dreier, Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Duke University [Durham], and Royal Institute of Technology [Stockholm] (KTH )
- Subjects
Fetal Proteins ,0301 basic medicine ,actin cytoskeleton ,Green Fluorescent Proteins ,Cell ,Formins ,Arp2/3 complex ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,macromolecular substances ,Mechanotransduction, Cellular ,Actin-Related Protein 2-3 Complex ,Basement Membrane ,Polymerization ,03 medical and health sciences ,Cell Movement ,Genes, Reporter ,Morphogenesis ,medicine ,Animals ,Secretion ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Actin ,Basement membrane ,Multidisciplinary ,biology ,Chemistry ,Microfilament Proteins ,force production ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,Cell Biology ,Biological Sciences ,cell invasion ,biology.organism_classification ,Actin cytoskeleton ,Actins ,Biomechanical Phenomena ,anchor cell ,Cell biology ,Luminescent Proteins ,Eukaryotic Cells ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Laminin - Abstract
Significance Basement membrane is a particular kind of sheet-like extracellular matrix that separates tissue compartments. Invasion of cells through basement membrane barriers is a key aspect of many normal and pathological processes, including organ development and cancer cell metastasis. Invasive protrusions are rich in actin, a cytoskeletal biopolymer, the self-assembly of which can produce force and remodel extracellular matrix. However, in the invasive protrusion, actin has been attributed a function in scaffolding and trafficking, and its mechanical role has not been explored. Here we show that invading cells in C. elegans apply forces via actin assembly to break through basement membrane, and that force production is one of the key features of invasion., 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.
- Published
- 2018