Involved researchers: Houssain BENABDELHAK, Bruno DASSY, Nicolas TAULIER, Wladimir URBACH

Rationale. Cell membranes and their associated transporters are essential for maintaining cellular survival and functionality. Acting as both a selective barrier and a platform for signal transduction, the membrane regulates the controlled exchange of substances required for life. Transporters embedded within the membrane enable precise molecular exchange, maintaining homeostasis and mediating cellular responses to environmental cues. Dysfunctions in these components are implicated in numerous diseases, highlighting their importance as therapeutic targets.

Mechanical stimuli drive a wide range of physiological processes, including touch sensation, nociception, auditory transduction, and blood pressure regulation. While the activity of mechanically activated (MA) ion channels has been widely documented in various cell types, the molecular identities of many MA channels remain elusive. Notably, pressure waves are known to activate MA channels. However, an intriguing question arises: can pressure waves also modulate the activity of proteins not traditionally activated by mechanical stimuli?

Proposed Solutions.  We investigate the effects of ultrasound on proteins whose activities are not mechanically induced. By integrating microbiological, biochemical, and biophysical techniques with in vitro, in vivo, and by molecular dynamics approaches, we aim to elucidate how ultrasound influences protein systems. Importantly, our experiments are designed to minimize thermal effects, focusing instead on the direct impact of pressure waves.

Our study centers on two bacterial systems relevant to antibiotic resistance in Escherichia coli: the efflux pump system AcrAB-TolC and the outer membrane porins OmpF and OmpC, which regulate substrates influx. These models provide a foundation for exploring ultrasound-mediated modulation of membrane transporters.

The methodologies and insights developed in this work have broader applications, including the study of membrane transporters involved in cancer cell chemoresistance. By advancing our understanding of ultrasound effects at the molecular level, this research will pave the way for more precise biological and medical tools, while minimizing the adverse effects typically associated with ultrasound exposure.