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. 2023 Mar 13;8(4):629–639. doi: 10.1038/s41564-023-01339-5

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 6 — We provide two hypotheses for potential means of activation of mechanosensitive ion channels in infected cells that may drive infected cell extrusion. Mechanosensitive ion channels such as Piezo1 can be activated by (a) external compression forces that induce membrane deformation, as well as (b) cell-intrinsic mechanical forces transmitted through tethered cytoskeletal filaments. (c, d) We present conceptual models for how viral infection may induce channel activation via both outside-in or cell-intrinsic forces. (c) In uninfected cells, cytoskeletal filaments provide structural support beneath the plasma membrane, reducing membrane deformation from cell-extrinsic forces. In infected cells wherein actin is rearranged, this structural support may be missing, resulting in ‘softer’ membranes more easily deformed by external compression forces. (d) In the force-through-filament model, cell-intrinsic mechanical forces are transmitted to Piezo channels via tethering to cytoskeletal filaments. In infected cells, cytoskeletal rearrangements may transmit forces directly to tethered Piezo channels, inducing activation. Adapted from ‘PIEZO Channels: How Do They Allow Mechanosensation?’, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates.