(721c) Dissecting the Active Gel Dynamics of the Microtubule Cytoskeleton in Living Epithelial Cells

Despite the central role of mechanics in many cellular processes, a complete mechanical picture of the cytoskeleton is lacking. In analogy with traditional polymer systems many studies have focused on cellular rheology but have been limited by the lack of observable molecular time scales. Recent studies have begun to examine the ATP-dependent, random stress fluctuations in cells due to polymerization forces and molecular motor activity. These experiments have largely been interpreted in terms of glassy materials or active gels. Here we characterize the stress and strain fluctuations in the interior of TC7 epithelial cells across six decades of frequency by combining two point microrheology and laser tracking microrheology. Then we ?dissect' the different physical mechanisms and corresponding molecular determinants that drive the fluctuating intracellular stresses with a combination of pharmacological treatments and mathematical modeling. We find rheology changes, spectral characteristics of the fluctuating stresses, relevant molecular time scales, and statistical behavior of particle displacements consistent with a mechanical picture of deep cell interior as a microtubule based polar, active gel.