Abstract
Phosphatidic acid (PA) is one of the simplest membrane phospholipids, yet it plays a crucial role in various biologically relevant processes that take place in cells. Since PA generation may be triggered by a variety of factors, very often of antagonistic character, the specific nature of physiological responses driven by PA is not clear. In order to shed more light on these issues, we carried out a systematic characterization of membranes containing one of the three biologically significant PA molecular species. The effect of these molecules on the properties of membranes composed of phosphatidylcholine and/or cholesterol was assessed in a multidisciplinary approach, including molecular dynamic simulations, flicker noise spectroscopy, and Langmuir monolayer isotherms. The first enables the determination of various macroscopic and microscopic parameters such as lateral diffusion, membrane thickness, and defect analysis. The obtained data revealed a strong interaction between unsaturated PA species and phosphatidylcholine. On the other hand, the behavior of saturated PA was greatly influenced by cholesterol. Additionally, a strong effect on mechanical properties was observed in the case of three-component systems, which could not be explained by the simple extrapolation of parameters of the corresponding two-component systems. Our data show that various PA species are not equivalent in terms of their influence on lipid mono- and bilayers and that membrane composition/properties, particularly those related to the presence of cholesterol, may strongly modulate PA behavior.
Highlights
IntroductionPhosphatidic acid (PA) is one of the simplest phospholipids
Accepted: 22 October 2021Phosphatidic acid (PA) is one of the simplest phospholipids
We focused on filling that void and characterized the membranes with phosphatidic acids such as POPA (16:0–18:1), DPPA (16:0–16:0), and SAPA (18:0–20:4)
Summary
Phosphatidic acid (PA) is one of the simplest phospholipids It is characterized by unique biophysical (physicochemical) properties: a small headgroup; negative charge and a phosphomonoester group. Its cellular content is rather small, as it is estimated to constitute about 1–4 mol% of all lipids It plays a crucial role in lipid metabolism, as it is used in the synthesis of all other types of glycerophospholipids and acts as a modulator of membrane shape [1,2]. It is an important second messenger, capable of binding and/or activating a broad range of effector proteins influencing their functionality [3]. It is worth underlining that recognition of lipidic components of membranes should not be interpreted as simple receptor-ligand binding events and take into account physicochemical properties of the membrane
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