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Cell sheet integrity and nanomechanical breakdown during programmed cell death

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Abstract

Apoptosis is a critical physiological pathway required for the normal functioning, homeostasis, and development of many organisms. This process is highly regulated at the biochemical level and has been intensively studied. Recent evidence has demonstrated that apoptosis is also a controlled nanomechanical process which relies on feedback between biochemical signaling and the nanomechanical properties of the microenvironment. Deregulation of the nanomechanical breakdown of apoptotic cells results in the poorly timed release of cells and cell debris that leads to the pathogenesis of several inflammatory diseases. In this study, we investigate the nanomechanical consequences of early apoptosis in human fibroblasts grown as single cells and as cell monolayers. These fibroblasts are found within the body and are involved in many processes including wound healing and repair in which apoptosis plays a major role. We find that although the cells undergo massive morphological remodeling and nanomechanical breakdown, the extra-cellular matrix (ECM) acts to maintain monolayer integrity. Via strong interactions between fibronectin and F-actin (fibronexus junctions), the ECM maintains and reinforces cell monolayers during breakdown. This study sheds new insights on our understanding of apoptosis and how biological systems utilize multiple inter- and intra-cytoarchitectures to regulate nanomechanical breakdown.

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Acknowledgments

We thank the Natural Sciences and Engineering Research Council (NSERC) and the Canada Research Chairs Program for support of this study. JW gratefully acknowledges the University of Ottawa NSERC CREATE Quantitative Biomedicine Program for a summer fellowship.

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  1. Department of Physics, MacDonald Hall, University of Ottawa, 150 Louis Pasteur, Ottawa, ON, K1N 6N5, Canada

    Jiashan Wang & Andrew E. Pelling

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  1. Jiashan Wang
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  2. Andrew E. Pelling
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Correspondence to Andrew E. Pelling.

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Wang, J., Pelling, A.E. Cell sheet integrity and nanomechanical breakdown during programmed cell death. Med Biol Eng Comput 48, 1015–1022 (2010). https://doi.org/10.1007/s11517-010-0640-z

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