Mechanotransduction as an Adaptation to Gravity

Abstract

Gravity has played a critical role in the development of terrestrial life. A key event in evolution has been the development of mechanisms to sense and transduce gravitational force into biological signals. The objective of this manuscript is to review how living organisms on Earth use mechanotransduction as an adaptation to gravity. Certain cells have evolved specialized structures, such as otoliths in hair cells of the inner ear and statoliths in plants, to respond directly to the force of gravity. By conducting studies in the reduced gravity of spaceflight (microgravity) or simulating microgravity in the laboratory, we have gained insights into how gravity might have changed life on Earth. We review how microgravity affects prokaryotic and eukaryotic cells at the cellular and molecular levels. Genomic studies in yeast have identified changes in genes involved in budding, cell polarity, and cell separation regulated by Ras, PI3K, and TOR signaling pathways. Moreover, transcriptomic analysis of late pregnant rats have revealed that microgravity affects genes that regulate circadian clocks, activate mechanotransduction pathways, and induce changes in immune response, metabolism, and cells proliferation. Importantly, these studies identified genes that modify chromatin structure and methylation, suggesting that long-term adaptation to gravity may be mediated by epigenetic modifications. Given that gravity represents a modification in mechanical stresses encounter by the cells, the tensegrity model of cytoskeletal architecture provides an excellent paradigm to explain how changes in the balance of forces, which are transmitted across transmembrane receptors and cytoskeleton, can influence intracellular signaling pathways and gene expression.

The dynamic adaptation of primary human endothelial cells to simulated microgravity

“…A representative blot is shown. C ) HUVECs were transfected with siRNA against HSP70 or with a scrambled nonsilencing sequence (2) and maintained in the RWV or in CTR for 48 h. To assess silencing, real-time PCR was performed using primers designed on the HSPA1A sequence. D) Cells treated as in C were trypsinized and counted.…”

The resolution of ambiguity as the basis for life: A cellular bridge between Western reductionism and Eastern holism

“…The effects of microgravity inhibit calcium flux, and then, through complex cellular connections, its metabolism and ability to reproduce. In each instance, this fluctuation can be attributed to the loss of cytoskeletal control (Najrana and Sanchez-Esteban, 2016). Hence, all aspects of cellular organization and function are linked through reciprocating pathways.…”

“…For example, TOR, as an essential metabolic regulator, also controls actin polymerization, and is therefore an important determinant of cytoskeletal conformation (Johnson et al, 2015). If yeast is deprived of the normal environmental cues for polarity and budding, the effects reverberate across the cell through the cytoskeleton, resulting in changes in TOR-mediated metabolism and reproduction (Najrana T, Sanchez-Esteban, 2016). …”

Simulated microgravity triggers characteristic morphology and stress response in Saccharomyces cerevisiae

“…Statocytes sense gravity by the accumulation of statoliths in the direction of the gravity vector (Morita & Tasaka, ), resulting in relocation of the plant hormone, auxin, which plays a role in plant elongation and rooting tip toward the gravity vector (Perbal & Driss‐Ecole, ). In addition to these effects on plant cells, the change in gravity also affects gene expression, growth, and morphogenesis in many unicellular and multicellular organisms (Najrana & Sanchez‐Esteban, ). As a result, the effects of gravity have been investigated in many prokaryotic and eukaryotic cells.…”