Simulating Life in Space to Understand Life on Earth

A new study performed by four departments at Sapienza University, together with the University of Campania and the ISS employed a highly innovative system to analyse the effect of the absence of gravity on cell life. The results, published on Nature NPJ Microgravity, reveal the importance of biophysical factors in the definition of new therapeutic strategies against cancer

The force of gravity is an essential component of Earth and, notwithstanding its weakness compared to the electromagnetic interactions that govern the chemical reactions at the basis of life, it exerts a strong influence even at the molecular level.

A new study carried out in collaboration by four departments at Sapienza University (Dept. of Experimental Medicine, “Pietro Valdoni” Surgery Dept., Dept. of Molecular Medicine and Dept. of Anatomical, Histological, Medical-Legal and Locomotor Apparatus Sciences) together with the “Luigi Vanvitelli” University of Campania and the Istituto Superiore di Sanità, observed what happens to cells when cultured in simulated microgravity (weightlessness).

Results, published on Nature NPJ Microgravity, reveal that loss of gravity, which is always present during the evolution of organisms, has an effect on cell structure and phenotype. However, although cells behavior was found to be dramatically altered, genome pattern expression did not change significantly and cells still preserve their genetic identity.

The research team employed a highly sophisticated and innovative device – a Random Positioning Machine-RPM - to simulate microgravity on ground, thus reproducing the gravity environment of the International Space Station.

Microgravity is a particular condition in which a system is subjected to an extremely weak gravitational field. Such a condition is instrumental to identify a number of factors, which are usually masked by a strong gravitational field, namely by recognizing the effects of pure, physical factors in driving cell fate commitment.

In medical research, it is known that microgravity can perturb the fundamental mechanisms of biological processes, and these weightlessness-based studies are used to investigate both the effects on astronauts’ permanence in space and the mechanisms involved in “terrestrial” pathologies.

The research group coordinated by Prof. Mariano Bizzarri from the Sapienza Department of Experimental Medicine and composed by Elisabetta Ferretti, Agnese Po, Alessandro Giuliani, Maria Grazia Masiello, Alessandra Cucina, Angela Catizone, Giulia Ricci, Martina Chiacchiarini and Marco Tafani, observed breast tumour cells (MCF7) and their behaviour in absence of gravity.

“We noticed,” explains Prof. Bizzarri, “a change in the cell phenotype, which immediately separated into two completely different-looking populations. However, once the cellular system was returned to normal gravitational conditions, the changes disappeared, revealing the transitory nature of these variations and the limited impact on the identity of the cellular system.”

The team employed mathematical and statistical methods to analyse the variation of the gene expression of the different populations. The trigonometric-based approach allowed the researchers to address the different genetic profiles as points on a trajectory in angular space and the positions occupied inside them by different cellular systems as the new “adaptive” states. The study has revealed that in the absence of gravity the same genotype can give rise to different phenotypes, demonstrating that living systems can adapt themselves through reduction in their degree of freedom.

“Although the genotype does not change,” explains Elisabetta Ferretti from the Department of Experimental Medicine, “two very different cell types emerge in terms of shape and motility. In particular, given that some prominent cancer characteristics, such as invasiveness and the ability to migrate, are nullified by microgravity, our observations allow us to infer that the same could be achieved on Earth if the physical micro-environment of the cancer cells was conveniently treated. This result shows that the biophysics of cancer may be useful to develop a different therapeutic strategy aiming to modify the micro-environment even before the cells themselves. Secondly, the fact that the absence of gravity interferes with cell replication and differentiation raises questions on the possibility of normal embryonic development in space.”

References:

Phenotypic transitions enacted by simulated microgravity do not alter coherence in gene transcription profile - Agnese Po, Alessandro Giuliani, Maria Grazia Masiello, Alessandra Cucina, Angela Catizone, Giulia Ricci, Martina Chiacchiarini, Marco Tafani, Elisabetta Ferretti & Mariano Bizzarri - npj Microgravity volume 5, Article number: 27 (2019) DOI https://doi.org/10.1038/s41526-019-0088-x