Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects
Date
2017
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Abstract
This study presents two novel theoretical models to elucidate frequency sensitive nuclear mechanisms in low-intensity ultrasound enhanced bioeffects. In contrast to the typical 1.5 MHz pulsed ultrasound regime, our group previously experimentally confirmed that ultrasound stimulation of anchored chondrocytes at resonant frequency maximized gene expression of load inducible genes which are regulatory markers for cellular response to external stimuli. However, ERK phosphorylation displayed no frequency dependency, suggesting that the biochemical mechanisms involved in enhanced gene expression is downstream of ERK phosphorylation. To elucidate such underlying mechanisms, this study presents a theoretical model of an anchored cell, representing an in vitro chondrocyte, in an ultrasound field. The model results showed that the mechanical energy storage is maximized at the chondrocyte’s resonant frequency and the energy density in the nucleus is almost twice as high as in the cytoplasm. Next, a mechanochemical model was developed to link the mechanical stimulation of ultrasound and the increased mechanical energy density in the nucleus to the downstream targets of the ERK pathway. This study showed for the first time that ultrasound stimulation induces frequency dependent gene expression as a result of altered rates of transcription factors binding to chromatin.
Description
CITATION: Miller, A. D., et al. 2017. Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects. PLoS ONE, 12(8):e0181717, doi:10.1371/journal.pone.0181717.
The original publication is available at https://journals.plos.org/plosone
The original publication is available at https://journals.plos.org/plosone
Keywords
Ultrasound stimulation, Biochemical markers, Biochemical genetics, Phosphorylation, Ultrasound stimulation, Genetic regulation, Genetic expression
Citation
Miller, A. D., et al. 2017. Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects. PLoS ONE, 12(8):e0181717, doi:10.1371/journal.pone.0181717