Membrane curvature induces cardiolipin sorting

Elena Beltrán-Heredia,Feng-Ching Tsai,Patricia Bassereau,Samuel Salinas-Almaguer,Francisco Monroy,Francisco J Cao

doi:10.1038/s42003-019-0471-x

Abstract

Cardiolipin is a cone-shaped lipid predominantly localized in curved membrane sites of bacteria and in the mitochondrial cristae. This specific localization has been argued to be geometry-driven, since the CL’s conical shape relaxes curvature frustration. Although previous evidence suggests a coupling between CL concentration and membrane shape in vivo, no precise experimental data are available for curvature-based CL sorting in vitro. Here, we test this hypothesis in experiments that isolate the effects of membrane curvature in lipid-bilayer nanotubes. CL sorting is observed with increasing tube curvature, reaching a maximum at optimal CL concentrations, a fact compatible with self-associative clustering. Observations are compatible with a model of membrane elasticity including van der Waals entropy, from which a negative intrinsic curvature of −1.1 nm−1 is predicted for CL. The results contribute to understanding the physicochemical interplay between membrane curvature and composition, providing key insights into mitochondrial and bacterial membrane organization and dynamics.

Highlights

Cardiolipin is a cone-shaped lipid predominantly localized in curved membrane sites of bacteria and in the mitochondrial cristae
The CL molecule is composed of two phosphatidic acids linked together by a short glycerol bridge, which results in a conical shape with a smaller cross-sectional area in the polar head relative to the hydrophobic tails
Membranes nanotubes of controlled radii were pulled out from GUVs made of the biomimetic mixture egg phosphatidylcholine (EPC)/CL

Summary

Introduction

Cardiolipin is a cone-shaped lipid predominantly localized in curved membrane sites of bacteria and in the mitochondrial cristae. CL participates in the binding of some peripheral proteins placed on these highly curved regions[7] These facts are suggestive for a possible role of CL in bacterial cell shaping[4,5], no evidence of its essential contribution to cell division has been raised from experiments. CL-enriched cristae domains is customary assumed to be geometry-driven[13]; arguably, a coupling between CL curvature and local composition would optimize the bending elasticity of the mitochondrial membrane. Due to their small size relative to proteins, lipids alone are generally not expected to be curvature sensitive except for in very particular conditions[14,15].

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Conclusion