Forcing contact inhibition of locomotion

Contact inhibition of locomotion drives a variety of biological phenomenon, from cell dispersion to collective cell migration and cancer invasion. New imaging techniques have allowed contact inhibition of locomotion to be visualised in vivo for the first time, helping to elucidate some of the molecules and forces involved in this phenomenon

Michael Abercrombie: contact inhibition of locomotion and more

Michael Abercrombie is regarded as one of the principal pioneers of cell biology. Although Abercrombie began his career as an experimental embryologist, working on the avian organizer with C. H. Waddington, questions on how cells in culture migrate and interact dominated his career. Whilst studying the social behaviour of chick heart embryonic fibroblasts, Abercrombie identified a phenomenon whereby colliding cells collapse their protrusions towards the cell-cell contact upon a collision, preventing their continued migration. The cells then form protrusions away from the contact and, space permitting, migrate away from each other. This behaviour is now referred to as ‘contact inhibition of locomotion’ and has been identified within embryology as the driving force behind the directional migration of the neural crest and the dispersion patterning of haemocytes and Cajal-Retzius neurons. Furthermore, its loss between collisions of cancer cells and healthy cells is associated with metastasis. In this review we begin with an overview of Abercrombie’s life and highlight some of his key publications. We then discuss Abercrombie’s discovery of contact inhibition of locomotion, the roles which cell-cell adhesions, cell-matrix adhesions and the cytoskeleton play in facilitating this phenomenon, and the importance of contact inhibition of locomotion within the living organism

The role and regulation of cell matrix adhesions during contact inhibition of locomotion

Contact inhibition of locomotion (CIL) was first characterised over 60 years ago and defined as the behaviour of a cell to cease its continued migration in the same direction upon a collision with another cell. It has been implicated in multiple developmental processes including the precise dispersion of haemocytes and the directional migration of the cranial neural crest. In addition its absence has been linked to metastasis in cancer. Although many molecular mechanisms have recently been implicated in CIL, the role of cell-matrix adhesions (CMAs) during this process remains unknown. It has been hypothesised that cellular forces play an important role in CIL; however the role of traction forces generated via CMAs and intercellular tension during CIL is unclear. In this present study neural crest cells are used to elucidate the role and regulation of CMAs during CIL. The findings presented here demonstrate a rapid disassembly of CMAs near the cell-cell contact between colliding cells. This disassembly is shown to be dependent upon the formation of N-cadherin based cellcell adhesions and driven by Src and FAK kinase activity. Furthermore this rapid disassembly of CMAs during CIL leads to a redistribution of intercellular forces from the substrate to the cell-cell contact and is essential to drive cell-cell separation after a collision

Redistribution of Adhesive Forces through Src/FAK Drives Contact Inhibition of Locomotion in Neural Crest

Contact inhibition of locomotion is defined as the behavior of cells to cease migrating in their former direction after colliding with another cell. It has been implicated in multiple developmental processes and its absence has been linked to cancer invasion. Cellular forces are thought to govern this process; however, the exact role of traction through cell-matrix adhesions and tension through cell-cell adhesions during contact inhibition of locomotion remains unknown. Here we use neural crest cells to address this and show that cell-matrix adhesions are rapidly disassembled at the contact between two cells upon collision. This disassembly is dependent upon the formation of N-cadherin-based cell-cell adhesions and driven by Src and FAK activity. We demonstrate that the loss of cell-matrix adhesions near the contact leads to a buildup of tension across the cell-cell contact, a step that is essential to drive cell-cell separation after collision

Transfer printing of AlGaInAs/InP etched facet lasers to Si substrates

InP-etched facet ridge lasers emitting in the optical C-band are heterogeneously integrated on Si substrates by microtransfer printing for the first time. 500 μm × 60 μm laser coupons are fabricated with a highly dense pitch on the native InP substrate. The laser epitaxial structure contains a 1-μm-thick InGaAs sacrificial layer. A resist anchoring system is used to restrain the devices while they are released by selectively etching the InGaAs layer with FeCl3:H2O (1:2) at 8 °C. Efficient thermal sinking is achieved by evaporating Ti-Au on the Si target substrate and annealing the printed devices at 300 °C. This integration strategy is particularly relevant for lasers being butt coupled to polymer or silicon-on-insulator (SOI) waveguides