Lipid Monolayers As a Model of the Interfacial Boundary of the Inner Mitochondrial Membrane

Abstract

Langmuir monolayers are a convenient model system for studying some processes occurring at the interface of the inner mitochondrial membrane (IMM). This review summarizes current scientific data on the use of monolayers to model the IMM, with an emphasis on the role of cardiolipin, a unique phospholipid with four acyl chains and two phosphate groups, which plays a key role in IMM structure formation and in the function of oxidative phosphorylation enzymes, and possibly in stabilizing protons at the interface and in their transfer from proton pumps to ATP synthase. The review discusses the advantages of monolayer systems over classical models: the ability to control the degree of lipid compression, the larger interfacial area, and compatibility with almost all detection methods. The key features of cardiolipin in monolayers are described in detail: conical molecular geometry, pH-dependent phase transitions, sensitivity to divalent cations (in particular, calcium), domain formation, and interactions with other components of the membrane/monolayer. Despite the good applicability of monolayer systems, limitations arise because the one-dimensional structure of a monolayer cannot fully reproduce IMM properties. A strategy for further development of monolayer model systems is proposed, including the use of lyso-forms of cardiolipin to optimize molecular geometry, the control of oxidative damage to polyunsaturated lipids, experiments at low pH and physiological ion concentrations, and the application of modern methods for proton generation at the interface (photoacids, or molecules that release protons upon illumination).