Sonomechanobiology: Vibrational stimulation of cells and its therapeutic implications

Abstract

All cells possess an innate ability to respond to a range of mechanical stimuli through their complex internal machinery. This comprises various mechanosensory elements that detect these mechanical cues and diverse cytoskeletal structures that transmit the force to different parts of the cell, where they are transcribed into complex transcriptomic and signaling events that determine their response and fate. In contrast to static (or steady) mechanostimuli primarily involving constant-force loading such as compression, tension, and shear (or forces applied at very low oscillatory frequencies ( ≤ 1 Hz) that essentially render their effects quasi-static), dynamic mechanostimuli comprising more complex vibrational forms (e.g., time-dependent, i.e., periodic, forcing) at higher frequencies are less well understood in comparison. We review the mechanotransductive processes associated with such acoustic forcing, typically at ultrasonic frequencies ( > 20 kHz), and discuss the various applications that arise from the cellular responses that are generated, particularly for regenerative therapeutics, such as exosome biogenesis, stem cell differentiation, and endothelial barrier modulation. Finally, we offer perspectives on the possible existence of a universal mechanism that is common across all forms of acoustically driven mechanostimuli that underscores the central role of the cell membrane as the key effector, and calcium as the dominant second messenger, in the mechanotransduction process.

Pulsed surface acoustic waves accelerate wound healing and reveal new parameter limits for cell stimulation in vitro

“…Pulse durations shorter than τ c = 100 ms may not yet be able to evoke any permanent responses in the cells. This would be a contradiction to Ambattu and Yeo's suggestion that the underlying mechanism of SAW stimulation is independent of the SAW signal's characteristics [14], because our results show a so far unknown limit of signal parameters for dynamically modulated signals with a critical pulse width as lower limit.…”

“…All studies on SAW stimulation reviewed by Ambattu and Yeo have relatively long exposure times to the SAW signal in the range of minutes to days [14]. Based on our results, it could be possible that the here mentioned underlying mechanisms of SAW stimulation are only activated by longer exposures to SAW.…”

“…In their recent review, Ambattu and Yeo proposed intracellular calcium mobilization and the cell membrane as universal key players in the mechanotransduction process of surface acoustic wave stimulation [14]. If the membrane tension is altered by high-frequency mechanical pressure or shear forces generated by acoustic streaming, cells can form vacuoule/vesicle-like dilations to counteract these deformations and activate transmembrane proteins like piezo channels [34].…”

“…This can help regulate the transmission of the mechanic force through the cell [35]. As a second messenger, the mechanic compression can drive the influx of Ca 2+ [36], whereas Ca 2+ mobilization is dependent on the SAW frequencies and exposure times and can evoke a variety of other signal cascades [14].…”

“…An understanding of the effects of different SAW signals on the wound healing behavior could help unravel the underlying mechanisms of SAW stimulation. In this context, Ambattu and Yeo also recently stated that understanding the mechanotransduction mechanisms could advance the SAW stimulation method in the clinical field [14]. Although in vivo systems are more complex than in vitro 2D wound healing models, an explanation of the stimulation effect in vitro could yield essential information on the underlying cellular mechanisms triggered by acoustic stimulation in general.…”