title: Epithelial Cell Packing Induces Distinct Modes of Cell Extrusions.
abstract: The control of tissue growth, which is a key to maintain the protective barrier function of the epithelium, depends on the balance between cell division and cell extrusion rates [1, 2]. Cells within confluent epithelial layers undergo cell extrusion, which relies on cell-cell interactions [3] and actomyosin contractility [4, 5]. Although it has been reported that cell extrusion is also dependent on cell density [6, 7], the contribution of tissue mechanics, which is tightly regulated by cell density [8-12], to cell extrusion is still poorly understood. By measuring the multicellular dynamics and traction forces, we show that changes in epithelial packing density lead to the emergence of distinct modes of cell extrusion. In confluent epithelia with low cell density, cell extrusion is mainly driven by the lamellipodia-based crawling mechanism in the neighbor non-dying cells in connection with large-scale collective movements. As cell density increases, cell motion is shown to slow down, and the role of a supracellular actomyosin cable formation and its contraction in the neighboring cells becomes the preponderant mechanism to locally promote cell extrusion. We propose that these two distinct mechanisms complement each other to ensure proper cell extrusion depending on the cellular environment. Our study provides a quantitative and robust framework to explain how cell density can influence tissue mechanics and in turn regulate cell extrusion mechanisms.
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.
authors.forename: Leyla
authors.initials: L
authors.lastname: Kocgozlu
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.|National University of Singapore Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, 117456, Singapore.
authors.forename: Thuan Beng
authors.initials: TB
authors.lastname: Saw
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.|National University of Singapore Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, 117456, Singapore.
authors.forename: Anh Phuong
authors.initials: AP
authors.lastname: Le
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.
authors.forename: Ivan
authors.initials: I
authors.lastname: Yow
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.
authors.forename: Murat
authors.initials: M
authors.lastname: Shagirov
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.
authors.forename: Eunice
authors.initials: E
authors.lastname: Wong
authors.affiliation: Institut Jacques Monod (IJM), CNRS UMR 7592 & Université Paris Diderot, 15 rue Hélène Brion, 75013, Paris, France.
authors.forename: René-Marc
authors.initials: RM
authors.lastname: Mège
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.|Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Block E4, #04-08, 4 Engineering Drive 3, 117583, Singapore.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.|Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543, Singapore.|Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604, Singapore.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Mechanobiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, 117411, Singapore.|Institut Jacques Monod (IJM), CNRS UMR 7592 & Université Paris Diderot, 15 rue Hélène Brion, 75013, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
mesh_terms: D000818:Animals; D002450:Cell Communication; D002452:Cell Count; D004285:Dogs; D004847:Epithelial Cells / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells
keywords: actin cytoskeleton; actomyosin purse-string; apoptosis; cell density; cell extrusion; epithelial cells; lamellipodium; mechanobiology