The role of the cytoskeleton in sensing changes in gravity by nonspecialized cells

Abstract

A large body of evidence indicates that single cells in vitro respond to changes in gravity, and that this response might play an important role for physiological changes at the organism level during spaceflight. Gravity can lead to changes in cell proliferation, differentiation, signaling, and gene expression. At first glance, gravitational forces seem too small to affect bodies with the size of a cell. Thus, the initial response to gravity is both puzzling and important for understanding physiological changes in space. This also offers a unique environment to study the mechanical response of cells. In the past 2 decades, important steps have been made in the field of mechanobiology, and we use these advances to reevaluate the response of single cells to changes in gravity. Recent studies have focused on the cytoskeleton as initial gravity sensor. Thus, we review the observed changes in the cytoskeleton in a microgravity environment, both during spaceflight and in ground-based simulation techniques. We also evaluate to what degree the current experimental evidence supports the cytoskeleton as primary gravity sensor. Finally, we consider how the cytoskeleton itself could be affected by changed gravity. To make the next step toward understanding the response of cells to altered gravity, the challenge will be to track changes quantitatively and on short timescales.

Signal Transduction in Primary Human T Lymphocytes in Altered Gravity During Parabolic Flight and Clinostat Experiments

“…Comparing the weight of a single cell with the other physical forces within a cell, it is unlikely that the cell can detect the vector of gravity. Searching for the initial gravity sensor, research has been focusing mainly on the cytoskeleton [47]. A popular model for how cells can sense mechanical forces (and possibly gravitational changes) is the idea that the cell cytoskeleton is built in tensegrity architecture, which provides the cell's stability.…”

Phenotypic Switch Induced by Simulated Microgravity on MDA-MB-231 Breast Cancer Cells

“…The balance between tensional forces and the cytoskeleton architecture modulates thereupon several complex cell functions like apoptosis, differentiation, proliferation, ECM remodelling, and so forth [31]. Compelling data demonstrated that both simulated and real, space-based microgravity can severely affect cytoskeleton structure and function [8, 32]. The most impressive modifications were observed in nonadherent RPM-exposed cells in which stress fibers disappear and actin architecture is severely compromised, thus jeopardizing the chances of cell anchoring to the substrate.…”

“…Similarly, relevant modifications in tissue organization have been recorded in microgravity-exposed organs and/or animals [5, 6]. Shape changes are likely to be mediated by concomitant structural rearrangement of cytoskeleton (CSK), which is severely disorganized under microgravity [7, 8]. CSK conveys mechanical signals into the cells, and by that way it influences both biochemical pathways [9, 10] and gene expression [11, 12].…”

Effects of Simulated Microgravity on Functions of Neutrophil-like HL-60 Cells

“…These results provide an insight how altered gravity regulates the functions of neutrophils and the underlying mechanisms which mediate the innate immune responses for long-term, manned spaceflight. Grenon et al 2013; bFGF ↓ HDTBR, head-down-tilt bed rest; RWV, rotating wall vessel (i.e., RCCS used in the current work); RPM, random positioning machine IL, interleukin; G-CSF, granulocyte-macrophage colony-stimulating factor; MIP-1α, macrophage inflammatory protein-1α; MCP-1, monocyte chemotactic protein 1; TNF-α, tumour necrosis factor-α; IFN-γ , Interferon-γ ; TGF-β, transforming growth factor-β; bFGF, basic fibroblast growth factor LFA-1, lymphocyte function-associated antigen-1; Mac-1, macrophage-1 antigen; ICAM-1, VLA-4, very late antigen 4; PSGL-1, P-selectin glycoprotein ligand 1; ICAM-1, intercellular cell adhesion molecule-1; PECAM-1, platelet/endothelial cell adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1 NO, nitric oxide; eNOS, endothelial nitric oxide synthase H 2 O 2 , hydrogen peroxide; ROS, reactive oxygen species Legend: ↑, increased; ↓, decreased; -, unchanged The cytoskeletal proteins have been proposed as potential gravity sensor, and significant changes of cytoskeletal network have been observed under microgravity environment both during spaceflight and in ground-based simulation techniques (Vorselen et al 2014). Although we have not seen obvious disorganization of the F-actin under the effects of simulated microgravity, the cell shape changes of HL-60 cells (Fig.…”