Mechanotransduction of Ultrasound is Frequency Dependent Below the Cavitation Threshold

Tobias M. Louw, Gaurav Budhiraja, Hendrik J. Viljoen, Anuradha Subramanian

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


This study provides evidence that low-intensity ultrasound directly affects nuclear processes, and the magnitude of the effect varies with frequency. In particular, we show that the transcriptional induction of first load-inducible genes, which is independent of new protein synthesis, is frequency dependent. Bovine chondrocytes were exposed to low-intensity (below the cavitational threshold) ultrasound at 2, 5 and 8 MHz. Ultrasound elevated the expression of early response genes c-Fos, c-Jun and c-Myc, maximized at 5 MHz. The phosphorylated ERK inhibitor PD98059 abrogated any increase in c-series gene expression, suggesting that signaling occurs via the MAPPK/ERK pathway. However, phosphorylated ERK levels did not change with ultrasound frequency, indicating that processes downstream of ERK phosphorylation (such as nuclear transport and chromatin reorganization) respond to ultrasound with frequency dependence. A quantitative, biphasic mathematical model based on Biot theory predicted that cytoplasmic and nuclear stress is maximized at 5.2 ± 0.8 MHz for a chondrocyte, confirming experimental measurements.

Original languageEnglish (US)
Pages (from-to)1303-1319
Number of pages17
JournalUltrasound in Medicine and Biology
Issue number7
StatePublished - Jul 2013


  • Biphasic mathematical model
  • Cell biomechanics
  • Load-inducible genes
  • Low-intensity ultrasound
  • Resonance

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Biophysics
  • Acoustics and Ultrasonics


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