High Frequency MHz-Order Vibration Enables Cell Membrane Remodelling and Lipid Microdomain Manipulation

We elucidate the mechanism underpinning a recently discovered phenomenon in which cells, quite unexpectedly, 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 remodelling of its lipid structure. In particular, the increase and hence 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 mobilise influx of calcium (Ca2+) ions into the cell. It is such modulation of this second messenger that is responsible for the downstream signalling and cell fates that ensue. Additionally, 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.