Abstract
Characterizing the elastic and dissipative properties of cells is not only necessary to determine how they deform, but also to fully understand how external mechanical forces trigger biochemical-signaling cascades to govern their behavior. Presently mechanical properties are largely assessed by applying local shear or compressive forces on single cells in isolation grown on non-physiological 2D surfaces. In comparison, our microfabricated vacuum actuated stretcher measures tensile loading of 3D multicellular ‘microtissue’ cultures. With our approach, we assessed here the time-dependency of microtissue mechanics and quantified the spatial remodeling that follows step length changes. Unlike previous results from other micro-rheological techniques, stress relaxation and recovery in microtissues followed stretched exponential behaviors that shared similar amplitudes but differed in their dynamics. In that regard, relaxation time constants changed with an inverse power law with step size, while recovery rates were invariant. Pharmacological responses, however, indicated that the contributions of individual cytoskeletal elements did not qualitatively differ from our existing understanding of their roles. The elasticity and dissipation of microtissues were mainly determined by the actin cytoskeleton but also augmented by myosin motor activity and reduced by the presence of microtubules. These results were reflected in changes to remodeling dynamics and spatial distributions of the integrated strain field. This assessment of microtissues offers insights into how the collective behavior of cells and their cytoskeletal proteins generate the dynamic mechanical properties of tissues, which is necessary for a full understanding of how cell behaviors are regulated in both health and disease.