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Nuclear mechanics during and after constricted migration

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Abstract

Cell migration through very narrow spaces in tissues has been seen in both physiological and pathological contexts. For example, immune cells squeeze through the vasculature and the extracellular matrix to reach wound or disease sites, and similarly, cancer cells crawl through interstices in tissues to invade tumor-free regions. The bulky and stiff nucleus of a cell is a barrier to such constricted migration—with smaller pores exponentially more difficult for passage. Cells must actively deform their nuclei to squeeze through constrictions, and this involves the stress-generating cytoskeleton. Here we review: (1) nuclear structures and morphological regulation, (2) proposed mechanisms that drive constricted migration, (3) short-term consequences such as nuclear envelope (NE) rupture and DNA damage during such process, (4) biophysical factors that facilitate NE rupture, and (5) long-term consequences such as genomic variation caused by repetitive NE rupture. Both experimental results and modeling are provided with the intention to better understand constricted migration.

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Acknowledgments

The authors in this study were supported by the National Institutes of Health National Cancer Institute under Physical Sciences Oncology Center Award U54 CA193417, National Heart Lung and Blood Institute Award R21 HL128187, the US–Israel Binational Science Foundation, and National Science Foundation grant agreement CMMI 15-48571. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health nor the National Science Foundation. The authors declare no competing financial interests.

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Authors and Affiliations

  1. Physical Sciences Oncology Center at Pennsylvania (PSOC@Penn), University of Pennsylvania, Philadelphia, PA, 19104, USA

    Yuntao Xia, Charlotte R. Pfeifer & Dennis E. Discher

  2. Molecular and Cell Biophysics Lab, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Yuntao Xia, Charlotte R. Pfeifer & Dennis E. Discher

  3. Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Charlotte R. Pfeifer & Dennis E. Discher

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  1. Yuntao Xia
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Xia, Y., Pfeifer, C.R. & Discher, D.E. Nuclear mechanics during and after constricted migration. Acta Mech. Sin. 35, 299–308 (2019). https://doi.org/10.1007/s10409-018-00836-9

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