Sorting of Proteins and Lipids in Membrane Curvature and Composition Gradients

Abstract

The sorting of lipids and proteins in cellular membrane sorting centers such as the trans-Golgi network, the plasma membrane, and the endocytic recycling compartment, lies at the heart of fundamental biological phenomena such as organelle homeostasis, membrane signaling, and trafficking. Our research is directed at understanding biophysical contributions to the sorting of membrane components, using experimental lipid model membranes, and analytical thermodynamic and membrane elasticity theory.We will present measurements of thermodynamically reversible membrane curvature sensing for several peripherally binding membrane proteins, including toxins, endocytic accessory proteins, as well as naturally unfolded proteins. For example, whereas the cholera toxin subunit B is observed to partition away from regions of high positive membrane curvature, we show that the Epsin N-terminal homology domain enriches in such regions.Our recent research has furthermore shown that ideally diluted lipids are not significantly sorted in curvature gradients presented by a cylindrical membrane in contact with a large thermodynamic reservoir (a giant unilamellar vesicle). This finding is consistent with analytical theories as well as molecular dynamics simulations and indicates that lipid sorting needs to be amplified by cooperative interactions, as is indeed observed in vesicles composed of ternary lipid mixtures. Two regimes of cooperatively amplified curvature demixing are distinguished: a) the sorting in the weak segregation limit in compositions near a demixing phase boundary and b) the sorting in the strong segregation limit, deep in the coexistence region. We will describe both regimes by means of thermodynamic models and also discuss dynamic aspects of curvature sorting.