Direct current electric field suppresses NPFFR2 expression in macrophages and alters its predicted conformational...

Neuropeptide FF receptor 2 (NPFFR2) plays a role in bioelectric field regulation in bone marrow-derived macrophages (BMDMs), but the influence of electric fields on NPFFR2 protein behavior remains unclear. This study investigates the effects of direct current electric field (dcEF) stimulation on NPFFR2 through cellular experiments and molecular dynamics (MD) simulations. The findings revealed that after applying physiologically relevant dcEF intensities (50 and 200 mV/mm) to wild-type and Npffr2-knockout BMDMs, cell viability was not significantly affected, but notable morphological changes occurred in both cell types. The dcEF stimulation suppressed NPFFR2 protein expression and induced cytoskeletal rearrangement in wild-type BMDMs. Furthermore, transcriptomic analysis revealed extensive gene expression changes, while MD simulations demonstrated that NPFFR2 conformation is sensitive to electric field strength in an intensity-dependent manner. Overall, these findings provide new insights into the interplay between a physical stimulus and a key immune receptor, suggesting that dcEF may regulate macrophage function by altering NPFFR2 protein levels and conformational stability.