New research shows sound waves trigger cellular gene responses and suppress fat development
Researchers in Japan have demonstrated that acoustic waves in the audible frequency range can directly modulate gene expression in mammalian cells and significantly inhibit adipocyte differentiation. The study reveals a novel mechanotransduction pathway linking sound stimulation to cellular responses via focal adhesion signalling, opening potential applications in regenerative medicine and biotechnology.
Scientists at Kyoto University have uncovered compelling evidence that cells can perceive and respond to audible sound frequencies through specific molecular pathways. Using a direct sound emission system, the research team exposed murine C2C12 myoblasts to acoustic waves at 440 Hz, 14 kHz, and white noise at 100 Pa intensity, identifying dozens of genes whose expression levels changed significantly within hours of sound exposure.
Novel acoustic stimulation system reveals cellular sound sensitivity
The research, published in Communications Biology, employed an innovative experimental setup using a vibrational transducer to generate acoustic waves directly in cell culture medium. This approach eliminated confounding variables present in previous loudspeaker-based systems.
“Eukaryotic cells are equipped with multiple mechanosensory systems and perceive a wide range of mechanical stimuli from the environment. However, cell-level responses to audible range of acoustic waves, which transmit feeble yet highly frequent physical perturbations, remain largely unexplored,” the authors stated.
RNA sequencing analysis revealed 42 early-response genes after 2 hours of continuous sound emission, expanding to 145 genes after 24 hours. The researchers identified both frequency-specific and universal responses, with some genes showing consistent upregulation across all three sound patterns tested.
Focal adhesion pathway mediates sound-triggered gene responses
The molecular mechanism underlying cellular sound perception centres on focal adhesion kinase (FAK) activation and subsequent prostaglandin signalling. Sound stimulation triggered phosphorylation of FAK at tyrosine 397, leading to enhanced cell adhesion and morphological changes characterised by lamellipodial extension.
“The activation of prostaglandin-endoperoxide synthase 2/cyclooxygenase-2 (Ptgs2/Cox-2), a high and immediate sound-responding gene, is dependent on focal adhesion kinase activation and mediates sound-triggered gene responses by activating prostaglandin E2 synthesis,” the researchers reported.
Live cell imaging demonstrated that acoustic stimulation promoted cell edge expansion and increased adhesion area by 15-20% within one hour. When FAK phosphorylation was blocked using the specific inhibitor Y15, both morphological changes and gene responses were abolished, confirming FAK’s central role in acoustic mechanotransduction.
Sound waves suppress adipocyte differentiation through prostaglandin signalling
The study revealed particularly striking effects on adipocyte development. 3T3-L1 preadipocytes showed the highest sensitivity to acoustic stimulation among all cell types tested, exhibiting robust FAK phosphorylation, Ptgs2 expression, and prostaglandin E2 (PGE2) production.
Continuous acoustic stimulation during the critical differentiation period significantly suppressed adipocyte maturation. Cells exposed to 440 Hz sound for 72 hours showed dramatic reductions in key adipocyte markers, with CCAAT/enhancer-binding protein α (Cebpa) and peroxisome proliferator-activated receptor γ (Pparg) expression levels dropping to 0.18 and 0.26 respectively compared to controls.
Lipid accumulation analysis confirmed these molecular findings, with continuous sound exposure increasing the proportion of undifferentiated cells from 23% to 39%. Even periodic stimulation (2 hours daily for 3 days) achieved similar suppressive effects, suggesting potential therapeutic applications.
Cell-type specificity suggests targeted applications
The research demonstrated marked cell-type specificity in acoustic responses, with stromal and derivative cell types (fibroblasts, myoblasts, osteoblasts, and adipocytes) showing high sensitivity compared to epithelial and neuronal cells. This selectivity appears related to differences in focal adhesion structure and cellular motility characteristics.
“Adhesive stromal and its derivative cells, including fibroblasts, myoblasts, osteoblasts, and adipocytes, were highly sensitive to acoustic stimulation, possibly due to their highly adhesive and motile nature that is essential to develop active focal adhesions,” the authors noted.
Implications for therapeutic applications
The findings suggest acoustic stimulation could serve as a non-invasive tool for modulating cellular behaviour in therapeutic contexts. The ability to suppress adipocyte differentiation through controlled sound exposure may have applications in obesity treatment or tissue engineering approaches.
The research also provides mechanistic insights that distinguish audible frequency acoustic stimulation from ultrasonic therapies currently used clinically. Unlike low-intensity pulsed ultrasound (LIPUS) at MHz frequencies, audible sound waves activate focal adhesion-mediated pathways rather than previously described ERK or YAP signalling routes.
“Collectively, these findings redefine acoustic waves as cellular stimulators and provide new avenues for applying acoustic techniques in biosciences,” the authors concluded.
The work establishes fundamental principles for understanding how cells integrate acoustic information from their environment, potentially leading to novel biotechnological applications in regenerative medicine and cellular manipulation techniques.
Reference
Kumeta, M., Otani, M., Toyoda, M., & Yoshimura, S. H. (2025). Acoustic modulation of mechanosensitive genes and adipocyte differentiation. Communications Biology, 8, 595. https://doi.org/10.1038/s42003-025-07969-1
