Membrane rolling induced by bacterial toxins

Martin Berg Klenow*, Jonas Camillus Jeppesen, Adam Cohen Simonsen

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Abstrakt

Membrane curvature effects are important in numerous cellular processes and many membrane interacting proteins induce spontaneous curvature upon membrane binding. Shiga and cholera toxins both belong to the AB 5 family of toxins and consist of a toxic A subunit and a membrane-binding pentameric B subunit. Shiga and cholera toxins induce tubular membrane invaginations in cells and GUVs due to curvature effects and the toxins are known from MD simulations to induce curvature. Membrane invaginations have been linked to uptake of the toxins into cells. As a novel model system to experimentally characterize curvature-inducing proteins, we study the morphology induced in planar membrane patches. It was previously shown that annexins induce distinct morphologies in membrane patches including membrane rolling. In this study we show that the B subunits of Shiga and cholera toxins (STxB, CTxB) both induce roll-up of cell-sized membrane patches. Rolling starts from the free membrane edges of the patch and is completed within a few seconds. We characterize the branched roll morphology and find experimental estimates for the spontaneous curvature of the toxins based on the topography of rolls. The estimates are in agreement with previous MD simulations. We quantify the dynamics of rolling as induced by the toxins and demonstrate agreement with a theoretical model of the rolling dynamics. The model solves the equation of motion for a membrane roll and includes viscous drag and adhesion to the support. The results suggest that membrane rolling may be a general phenomenon displayed by many proteins that induce negative curvature in membranes with free edges.

OriginalsprogEngelsk
TidsskriftSoft Matter
Vol/bind16
Udgave nummer6
Sider (fra-til)1614-1626
ISSN1744-683X
DOI
StatusUdgivet - 2020

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