High-frequency microrheology reveals cytoskeleton dynamics in living cells

Abstract

19th IUPAB Congress / 11th EBSA Congress, British Biophys Soc, Edinburgh, SCOTLAND, JUL 16-20, 2017International audienceLiving cells are viscoelastic materials, with the elastic response dominating at long timescales (≳1 ms) 1. At shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells are scarce 2. Here, we develop high-frequency microrheology (HF-MR) to probe the viscoelastic response of living cells from 1Hz to 100 kHz. We report the viscoelasticity of different cell types and upon cytoskeletal drug treatments. At previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequency, providing a univocal mechanical fingerprint. Microrheology over a wide dynamic range up to the frequency of action of the molecular components provides a mechanistic understanding of cell mechanics. Living cells constantly exert and sense mechanical forces. The magnitude and rate of these forces vary according to organ, tissue and function, modulating the mechanical phenotype of cells. Cells' mechanical response is mainly due to the structural organization and dynamics of individual components of the cytoskeleton (CSK). This complex filament network, immersed in a crowded cytoplasm constantly perturbed by molecular motors, displays viscoelastic behaviors 3. Consequently, cells exhibit elastic (conservative) and viscous (dissipative) responses that are frequency-dependent. Microrheology quantifies the viscoelastic response by measuring forces in response to deformations 4 (active microrheology), or by tracking the spontaneous fluctuations of embedded or endogenous particles 5 (passive microrheology). Viscoealastic properties are then quantified by a frequency-dependent complex shear modulus G