We elucidate the mechanism underpinning a recently discovered phenomenon in which cells respond to MHz-order mechanostimuli. Deformations induced along the plasma membrane under these external mechanical cues are observed to decrease the membrane tension, which, in turn, drives transient and reversible remodeling of its lipid structure. In particular, the increase and consequent coalescence of ordered lipid microdomains leads to closer proximity to mechanosensitive ion channels—Piezo1, in particular—that, due to crowding, results in their activation to mobilize influx of calcium (Ca2+) ions into the cell. It is the modulation of this second messenger that is responsible for the downstream signaling and cell fates that ensue. In addition, we show that such spatiotemporal control over the membrane microdomains in cells—without necessitating biochemical factors—facilitates aggregation and association of intrinsically disordered tau proteins in neuroblastoma cells, and their transformation to pathological conditions implicated in neurodegenerative diseases, thereby paving the way for the development of therapeutic intervention strategies.

中文翻译：

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高频 MHz 级振动可实现细胞膜重塑和脂质微结构域操作


我们阐明了最近发现的细胞对 MHz 级机械刺激做出反应的现象的基础机制。观察到在这些外部机械线索下沿质膜诱导的变形会降低膜张力，这反过来又驱动其脂质结构的瞬态和可逆重塑。特别是，有序脂质微结构域的增加和随之而来的融合导致更接近机械敏感离子通道（尤其是 Piezo1），由于拥挤，导致它们被激活以动员钙 （Ca2+） 离子流入细胞。正是这个第二个信使的调节负责随之而来的下游信号传导和细胞命运。此外，我们表明，这种对细胞膜微结构域的时空控制——不需要生化因素——促进了神经母细胞瘤细胞中固有无序的 tau 蛋白的聚集和关联，以及它们转化为与神经退行性疾病有关的病理状况，从而为治疗干预策略的发展铺平了道路。