ABSTRACT
Cells sense and react on changes of the mechanical properties of their environment, and likewise respond to external mechanical stress applied to them. Whether the gravitational field, as overall body force, modulates cellular behavior is however unclear. Different studies demonstrated that micro- and hypergravity influences the shape and elasticity of cells, initiate cytoskeleton reorganization, and influence cell motility. All these cellular properties are interconnected, and contribute to forces that cells apply on their surrounding microenvironment. Yet, studies that investigated changes of cell traction forces under hypergravity conditions are scarce. Here we performed hypergravity experiments on 3T3 fibroblast cells using the Large Diameter Centrifuge at the European Space and Technology Centre (ESA-ESTEC). cells were exposed to hypergravity of up to 19.5g for 16 h in both the upright and the inverted orientation with respect to the g-force vector. We observed a decrease in cellular traction forces when the gravitational field was increased up to 5.4g, followed by an increase of traction forces for higher gravity fields up to 19.5g independent of the orientation of the gravity vector. We attribute the switch in cellular response to shear-thinning at low g-forces, followed by significant rearrangement and enforcement of the cytoskeleton at high g-forces.
SIGNIFICANCE The behavior of cells critically depend on the mechanical properties of their environment. For example external stresses and strains lead to decisions in cell differentiation as well as to collective-migration in metastasis. Gravity, as a permanently acting body force, is one of those externs stresses. We demonstrate the impact of gravitational challenges on forces that cells apply to their environment. We observed a switch in cellular response with a decrease in cell traction forces for low bypgrarayiv. conditions, followed by a significant increase in cell traction forces at higher g-level. This particular cellular response reflects a switch in croskeletal organization, similar to that observed for cells in fluids where shear forces act.