How lipid asymmetry influences membrane protein function

Every cell is surrounded by a plasma membrane, a vital component that serves as a barrier and a communication interface between the interior and exterior of the cell. The molecular structure of these membranes is highly diverse. Of particular interest is the uneven distribution of phospholipids, essential building blocks of membranes, across the membrane`s two layers. This asymmetry is thought to be crucial for effective communication and transport within the cell. However, current studies often rely on simplified, symmetrical models that fail to capture the complexity of real biological systems. Consequently, our understanding of plasma membrane functions lacks this key aspect. To address this gap, our collaborative project brings together expertise from three research groups in Austria, Germany, and the Czech Republic. We hypothesize that the performance of membrane proteins is closely linked to the unique stress patterns found in asymmetric cell membranes. These stress patterns are influenced by the structure and dynamics of the lipids as well as their uneven distribution within the membranes. Exploring this relationship, we aim to gain new insights into how these properties regulate protein behavior and overall membrane function. Our approach involves utilizing advanced computer simulations, solid-state NMR spectroscopy, and scattering techniques to construct and analyze realistic models of asymmetric membranes and study their interactions with key membrane proteins. Our investigation will initially focus on fundamental properties of these membranes, such as lipid arrangement, dynamics, and structural integrity, with a specific emphasis on bacterial lipids. Subsequently, we will explore how these properties impact interactions with two essential bacterial proteinsOmpLA and GlpGrepresenting different structural types of membrane proteins. By integrating these state-of-the-art methodologies, we aim to examine a wide range of temporal and spatial scales to gain detailed insights into the role of lipid asymmetry in cell membranes. Our discoveries have the potential to advance biotechnology and medicine significantly. For example, they may facilitate the development of targeted lipid-based therapies and biosensors responsive to specific lipid compositions within cell membranes.