TAT-RasGAP317-326 kills cells by targeting inner-leaflet–enriched phospholipids

TAT-RasGAP317–326 is a cell-penetrating peptide-based construct with anticancer and antimicrobial activities. This peptide kills a subset of cancer cells in a manner that does not involve known programmed cell death pathways. Here we have elucidated the mode of action allowing TAT-RasGAP317–326 to kill cells. This peptide binds and disrupts artificial membranes containing lipids typically enriched in the inner leaflet of the plasma membrane, such as phosphatidylinositol-bisphosphate (PIP2) and phosphatidylserine (PS). Decreasing the amounts of PIP2 in cells renders them more resistant to TAT-RasGAP317–326, while reducing the ability of cells to repair their plasma membrane makes them more sensitive to the peptide. The W317A TAT-RasGAP317–326 point mutant, known to have impaired killing activities, has reduced abilities to bind and permeabilize PIP2- and PS-containing membranes and to translocate through biomembranes, presumably because of a higher propensity to adopt an α-helical state. This work shows that TAT-RasGAP317–326 kills cells via a form of necrosis that relies on the physical disruption of the plasma membrane once the peptide targets specific phospholipids found on the cytosolic side of the plasma membrane.

A fast linear electro-optical effect in a non-chiral bent-core liquid crystal

We report on the observation of an electro-optical effect for a linear rotation of the optical axis as a function of the electric field in a tilted liquid crystalline smectic phase of an achiral bent-core compound, attributed to a spontaneous helical state in its SmCSPF phase.

Forcing-dependent dynamics and emergence of helicity in rotating turbulence

The effects of large-scale mechanical forcing on the dynamics of rotating turbulent flows are studied by means of direct numerical simulations, systematically varying the nature of the mechanical force in time. We find that the statistically stationary solutions of these flows depend on the nature of the forcing mechanism. Rapidly enough rotating flows with a forcing that has a persistent direction relative to the axis of rotation bifurcate from a non-helical state to a helical state despite the fact that the forcing is non-helical. We demonstrate that the nature of the mechanical force in time and the emergence of helicity have direct implications for the cascade dynamics of these flows, determining the anisotropy in the flow, the energy condensation at large scales and the power-law energy spectra that are consistent with previous findings and phenomenologies under strong and weak turbulence.