Temporal Integration of Weak Acoustic Stress Leads to Delayed Cellular Responses

Abstract

Sound is a pervasive physical stimulus with beneficial or adverse effects depending on exposure. While controlled sound-based interventions such as ultrasound have demonstrated clinical utility, epidemiological studies link chronic environmental noise to increased cardiovascular and metabolic risk. Despite these associations, how weak sound is sensed and integrated at the cellular level remains unclear. Here, we investigate cellular responsiveness to acoustic pulse-wave stimulation in human endothelial cells, using intracellular calcium changes as a readout of cellular activation. Cellular responses to acoustic stimulation were compared with over-threshold mechanical stimulation. Over-threshold mechanical stimulation induced immediate responses, whereas single sub-threshold acoustic exposures produced no detectable response. In contrast, sustained sub-threshold acoustic stimulation over minutes produced delayed activation, with onset times dependent on stimulus intensity. These results demonstrate that cells integrate weak physical inputs over time, revealing a delayed activation regime under sustained sub-threshold exposure.