Life on Earth has evolved under the constant impact of Earth’s gravity, defined as 1g. Some organisms, including plants and some ciliates, perceive the direction of the gravitational vector: the gravitational sensing machinery in these organisms is often characterised by cell dense materials that are thought to activate mechanosensitive ion channels. Individual cells from organisms that do not exhibit gravitropic behaviour can also experience changes in both form and function under conditions of microgravity, yet the molecular mechanisms that underpin such changes are not well understood. Our research is seeking to establish model systems to investigate these questions in ground-based studies that simulate microgravity. We have been assessing the role of force sensing pathways in cellular adaptations to simulated microgravity using highly mechanically responsive cells (cancer cells). Given the complexity of these human cells, their variant morphology and the isolation of these individual cells from their native environment we are supplementing these studies with investigation of the impact of simulated microgravity on more simple cellular systems such as erythrocytes and fission yeast. Our early results highlight the potential role of mechanosensors in regulating cellular adaptations to microgravity as well as the need to better understand the alterations in structural proteins that can also influence force sensing at the cellular level.