Mechanical Stretch Counteracts Hypomagnetic Field-Induced Changes in YAP Nuclear Localization in C2C12 Myoblasts

Abstract

The geomagnetic field (GMF) is a persistent environmental factor that influences biological processes. Reduced geomagnetic field exposure can alter cellular processes, but its effects on cellular mechanotransduction and responsiveness to mechanical stimulation remain poorly understood. Here, we developed an in vitro platform combining a programmable uniaxial stretching device with a mu-metal shielding chamber to independently manipulate mechanical stretch and magnetic field exposure. Using C2C12 myoblasts, we evaluated culture conditions and cyclic stretching parameters to identify a regimen that promoted nuclear localization of the mechanosensitive transcriptional coactivator yes-associated protein (YAP). We then compared cell and nuclear morphology and YAP nucleocytoplasmic localization under geomagnetic field (GMF) and hypomagnetic field (HMF; approximately 5 nT) conditions, with or without cyclic stretch. Under static conditions, HMF exposure increased cell and nuclear areas, promoted nuclear elongation, reduced nuclear circularity, and decreased the nuclear YAP level. Cyclic stretch induced nuclear alignment perpendicular to the stretching direction under both magnetic field conditions, without significantly altering cell or nuclear area or nuclear elongation. Importantly, cyclic stretch increased nuclear YAP localization under both GMF and HMF conditions, restoring it in HMF-exposed cells to levels comparable to those in stretched cells under GMF. These findings indicate that C2C12 myoblasts remain responsive to mechanical stimulation under HMF conditions and that cyclic stretch can counteract the HMF-associated reduction in nuclear YAP localization. Our platform provides a foundation for investigating how magnetic and mechanical cues jointly regulate myoblast behavior.