Abstract

The study of how mechanical forces may influence cell behavior via cytoskeleton remodeling is a relevant challenge of nowadays that may allow us to define the relationship between mechanics and biochemistry and to address the larger problem of biological complexity. An increasing amount of literature data reported that microgravity condition alters cell architecture as a consequence of cytoskeleton structure modifications. Herein, we are reporting the morphological, cytoskeletal, and behavioral modifications due to the exposition of a seminoma cell line (TCam-2) to simulated microgravity. Even if no differences in cell proliferation and apoptosis were observed after 24 hours of exposure to simulated microgravity, scanning electron microscopy (SEM) analysis revealed that the change of gravity vector significantly affects TCam-2 cell surface morphological appearance. Consistent with this observation, we found that microtubule orientation is altered by microgravity. Moreover, the confocal analysis of actin microfilaments revealed an increase in the cell width induced by the low gravitational force. Microtubules and microfilaments have been related to autophagy modulation and, interestingly, we found a significant autophagic induction in TCam-2 cells exposed to simulated microgravity. This observation is of relevant interest because it shows, for the first time, TCam-2 cell autophagy as a biological response induced by a mechanical stimulus instead of a biochemical one.

Highlights

  • An increasing number of experimental observations have demonstrated that tissue homeostasis could be strongly influenced and regulated by physical forces, such as the modulation of gravity vector

  • Cytoskeleton elements are likely candidates for force sensing and transduction processes. These biomechanical properties of cell cytoskeleton explain the capability to propagate a mechanical stimulus over long distances in living tissues and represent the basis of the intriguing hypothesis that many, if not all, reported changes in ion fluxes, protein phosphorylation, membrane potential changes, and so forth are provoked by a mechanical modification somewhere within the cell or on its membrane [60, 61]

  • This paper is in line with this theory and adds experimental data supporting the importance of mechanotransduction and cell behavior

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Summary

Introduction

An increasing number of experimental observations have demonstrated that tissue homeostasis could be strongly influenced and regulated by physical forces, such as the modulation of gravity vector. It is well known that microgravity exposure could strongly influence cytoskeleton organization [10,11,12,13,14,15,16,17] and it is commonly accepted that cellular tensegrity alteration in microgravity exposed cells could explain, at least in part, the conversion of a mechanical cue into a biological response In this regard, recent studies have revealed the importance of cytoskeletal integrity, such as F-actin and microtubules, in the physiological specific aspects of autophagy, and some papers described the capability of microgravity to induce autophagy in living cells [18,19,20,21,22]. Despite several studies suggested a tumor suppressive role for autophagy, other reports support the hypothesis that this process is instead exploited by cancer cells to prime their proliferation and promote their survival [23,24,25,26,27]

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