Modeling cell contractility responses to acoustic tweezing cytometry

Abstract

• Mechanochemical conversion is a key mechanism for cells to sense and respond to acoustic tweezing cytometry (ATC). • ATC parameters, especially ultrasound center frequency, significantly impact cell contractility responses. • It is large molecules, rather than small ions, that mediate the global responses to a local ATC stimulus. • The incorporation of visible stress fiber bundles into 2D models better recapitulates the experimental observations. • Cells on rigid substrates exhibit more traction force increases while cells on soft substrates are more sensitive to ATC. Acoustic tweezing cytometry (ATC) is a recently developed method for cell mechanics regulation. Targeted microbubbles, which are attached to integrins and subsequently the actin cytoskeleton, anchor, amplify and transmit the mechanical energy in an acoustic field inside the cells, eliciting prominent cytoskeleton contractile force increases in various cell types. We propose that a mechanochemical conversion mechanism is critical for the high efficiency of ATC to activate cell contractility responses. Our models predict key experimental observations. Moreover, we study the influences of ATC parameters (ultrasound center frequency, pulse repetition frequency, duty cycle, and acoustic pressure), cell areas, the number of ATC stimuli, and extracellular matrix rigidity on cell contractility responses to ATC. The simulation results suggest that it is large molecules, rather than small ions, that facilitate global responses to the local ATC stimulation, and the incorporation of visible stress fiber bundles improves the accuracy of modeling.