Two dominant timescales of cytoskeletal crosslinking in the viscoelastic response of the cytoplasm

Abstract

Cells precisely regulate their frequency-dependent viscoelastic properties in response to chemical and mechanical cues. We use optical trap-based active microrheology using intracellular probes to measure the cytoplasmic mechanical response of fibroblast and macrophage cells over a broad frequency range (∼0.02-350 Hz). Both cell types show similar frequency-dependent behavior, suggesting that the mechanisms that control the cell's mechanical response are general to many cell types. At frequencies above 1 Hz, the cytoplasmic mechanical behavior shows a broad distribution of relaxation timescales consistent with power-law mechanics. At low frequencies (<1 Hz), cells exhibit fluidlike behavior with distinct relaxation timescales, similar to that observed in reconstituted networks of transiently crosslinked actin filaments. The response across all frequencies can be captured by a mathematical model combining a power-law term with two crosslinker-unbinding terms. The two unbinding rates required to describe the low-frequency response suggest that the viscoelastic relaxation of the cytoplasm is governed either by multiple dominant crosslinkers or by a single crosslinker with multiple states.