Preprint Hypothesis Version 2 Preserved in Portico This version is not peer-reviewed

MRTF May Be the Missing Link in a Multiscale Mechanobiology Approach toward Macrophage Dysfunction in Space

Version 1 : Received: 28 June 2022 / Approved: 7 July 2022 / Online: 7 July 2022 (04:08:39 CEST)
Version 2 : Received: 18 July 2022 / Approved: 18 July 2022 / Online: 18 July 2022 (10:59:36 CEST)

How to cite: An, R. MRTF May Be the Missing Link in a Multiscale Mechanobiology Approach toward Macrophage Dysfunction in Space. Preprints 2022, 2022070106 (doi: 10.20944/preprints202207.0106.v2). An, R. MRTF May Be the Missing Link in a Multiscale Mechanobiology Approach toward Macrophage Dysfunction in Space. Preprints 2022, 2022070106 (doi: 10.20944/preprints202207.0106.v2).

Abstract

Macrophages exhibit impaired phagocytosis, adhesion, migration, and cytokine production in space, hindering their ability to elicit immune responses. Considering that the combined effect of spaceflight microgravity and radiation is multiscale and multifactorial in nature, it is expected that contradictory findings are common in the field. This theory paper reanalyzes research on the macrophage spaceflight response across multiple timescales from seconds to weeks, and spatial scales from the molecular, intracellular, extracellular, to the physiological. Key findings include time-dependence of both pro-inflammatory activation and integrin expression. Here, we introduce the time-dependent, intracellular localization of MRTF-A as a hypothetical confounder of macrophage activation. We discuss the mechanosensitive MRTF-A/SRF pathway dependence on the actin cytoskeleton/nucleoskeleton, microtubules, membrane mechanoreceptors, hypoxia, oxidative stress, and intracellular/extracellular crosstalk. By adopting a multiscale perspective, this paper provides the first mechanistic answer for a three-decade-old question regarding impaired cytokine secretion in microgravity—and strengthens the connection between the recent advances in mechanobiology, microgravity, and the spaceflight immune response. Finally, we hypothesize MRTF involvement and complications in treating spaceflight-induced cardiovascular, skeletal, and immune disease.

Keywords

mechanobiology; microgravity; macrophage; multiscale; MRTF; radiation

Subject

LIFE SCIENCES, Cell & Developmental Biology

Comments (1)

Comment 1
Received: 18 July 2022
Commenter: Rocky An
Commenter's Conflict of Interests: Author
Comment: Updated figure 1, added a new figure 2
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