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Cardiolipin Effects on Membrane Structure and Dynamics

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Max Planck Institute for Intelligent Systems, Heisenbergstr. 3, 70569 Stuttgart, Germany, and German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
*E-mail: [email protected]. Tel: 0049 6221 5451234. Fax: 0049 6551 5451482.
Cite this: Langmuir 2013, 29, 51, 15878–15887
Publication Date (Web):August 20, 2013
https://doi.org/10.1021/la402669z
Copyright © 2013 American Chemical Society
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    Abstract

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    Cardiolipin (CL) is a lipid with unique properties solely found in membranes generating electrochemical potential. It contains four acyl chains and tends to form nonlamellar structures, which are believed to play a key role in membrane structure and function. Indeed, CL alterations have been linked to disorders such as Barth syndrome and Parkinson’s disease. However, the molecular effects of CL on membrane organization remain poorly understood. Here, we investigated the structure and physical properties of CL-containing membranes using confocal microscopy, fluorescence correlation spectroscopy, and atomic force microscopy. We found that the fluidity of the lipid bilayer increased and its mechanical stability decreased with CL concentration, indicating that CL decreases the packing of the membrane. Although the presence of up to 20% CL gave rise to flat, stable bilayers, the inclusion of 5% CL promoted the formation of flowerlike domains that grew with time. Surprisingly, we often observed two membrane-piercing events in atomic force spectroscopy experiments with CL-containing membranes. Similar behavior was observed with a lipid mixture mimicking the mitochondrial outer membrane composition. This suggests that CL promotes the formation of membrane areas with apposed double bilayers or nonlamellar structures, similar to those proposed for mitochondrial contact sites. All together, we show that CL induces membrane alterations that support the role of CL in facilitating bilayer structure remodeling, deformation, and permeabilization.

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