Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

68-POS Board 68 Distinct Modes of Apoptotic Cell Extrusion Governed by Epithelia Packing Density Leyla Kocgozlu 1 , Thuan Saw 1,2 , Anh Phuong Le 1,2 , Ivan Yow 1 , Murat Shagirov 1 , Eunice Wong 1 , René- Marc Mège 3 , Chwee Teck Lim 1,2,4 , Yusuke Toyama 1 , Benoit Ladoux 1,3 . 1 Mechanobiology Institute (MBI), National University of Singapore (NUS), Singapore, Singapore, 2 National University of Singapore Graduate School of Integrative Sciences and Engineering (NGS), NUS, Singapore, Singapore, 3 Institut Jacques Monod (IJM), CNRS UMR 7592 & Université Paris Diderot, Paris, France, 4 Department of Biomedical Engineering, National University of Singapore (NUS), Singapore, Singapore. Unnecessary or pathological cells are usually removed from the epithelia by a highly controlled process called cell extrusion, which is important for normal tissue development and homeostasis. In the context of programmed cell death, the consensus is that the dying cell receives certain biochemical trigger, and signals to the neighbor cells to help squeeze (extrude) itself out via a acto-myosin purse-string mechanism. Here we show by confining an in vitro MDCK tissue on a micro-patterned surface that the rate of apoptotic cell extrusion increases with cell density, suggesting that mechanical cues are important for extrusion. By measuring tissue dynamics and using pharmaceutical drug perturbations, we further show that the mode of cell extrusion also switches from a more lamellipodia-driven to a more purse-string based mechanism (as commonly known in the literature) when tissue becomes more packed. Altogether, we propose that these two mechanisms work in tandem to ensure the progression of apoptotic cell extrusion under diverse conditions in vivo.

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