Gravity constraints drive biological systems toward specific organization patterns. Commitment of cell specification is constrained by physical cues

Different cell lineages growing in microgravity undergo a spontaneous transition leading to the emergence of two distinct phenotypes. By returning these populations in a normal gravitational field, the two phenotypes collapse, recovering their original configuration. In this review, we hypothesize that, once the gravitational constraint is removed, the system freely explores its phenotypic space, while, when in a gravitational field, cells are “constrained” to adopt only one favored configuration. We suggest that the genome allows for a wide range of “possibilities” but it is unable per se to choose among them: the emergence of a specific phenotype is enabled by physical constraints that drive the system toward a preferred solution. These findings may help in understanding how cells and tissues behave in both development and cancer.