Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies

Abstract

Cell membranes are very complex biological systems including a large variety of lipids and proteins. Therefore, they are difficult to extract and directly investigate with biophysical methods. For many decades, the characterization of simpler biomimetic lipid membranes, which contain only a few lipid species, provided important physico-chemical information on the most abundant lipid species in cell membranes. These studies described physical and chemical properties that are most likely similar to those of real cell membranes. Indeed, biomimetic lipid membranes can be easily prepared in the lab and are compatible with multiple biophysical techniques. Lipid phase transitions, the bilayer structure, the impact of cholesterol on the structure and dynamics of lipid bilayers, and the selective recognition of target lipids by proteins, peptides, and drugs are all examples of the detailed information about cell membranes obtained by the investigation of biomimetic lipid membranes. This review focuses specifically on the advances that were achieved during the last decade in the field of biomimetic lipid membranes mimicking the mammalian plasma membrane. In particular, we provide a description of the most common types of lipid membrane models used for biophysical characterization, i.e., lipid membranes in solution and on surfaces, as well as recent examples of their applications for the investigation of protein-lipid and drug-lipid interactions. Altogether, promising directions for future developments of biomimetic lipid membranes are the further implementation of natural lipid mixtures for the development of more biologically relevant lipid membranes, as well as the development of sample preparation protocols that enable the incorporation of membrane proteins in the biomimetic lipid membranes.

Reconstitution of Functional Integrin αIIbβ3 and Its Activation in Plasma Membrane-Mimetic Lipid Environments

“…These properties pose major challenges on reconstitution approaches as they affect homogeneity and solubilisation properties, which are directly related to reconstitution success and the quality of membrane models [ 18 , 19 , 28 ]. We were able to embed the αIIbβ3 transmembrane receptor into membrane environments with distinct physicochemical properties.…”

“…Here, we report the adaption of αIIbβ3 reconstitution protocol for QCM-D measurements in lipid environments that more closely resemble the plasma membrane. To mimic the external leaflet of the platelet plasma membrane, we used a ternary lipid system comprising cholesterol, sphingomyelin (SM) and an unsaturated phospholipid represented by 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) [ 25 , 28 ]. Modulating their respective ratios, we are able to tune the membrane properties based on available phase diagrams [ 29 , 30 , 31 ] to more fluid liquid disordered (Ld) phases, rigid liquid-ordered (Lo) phases or a coexistence of both (Ld/Lo) [ 9 ].…”

NMR spectroscopy of lipidic cubic phases

“…Dynamic interactions between membrane proteins and the lipid bilayer of cell membranes are responsible for stabilising membrane proteins and influence their folding, structure and function in vivo (Brown 2017). Consequently, the preservation of membrane protein integrity outside their native environment is a challenge and a range of model membrane systems have been used to study membrane proteins (Luchini and Vitiello 2021). As discussed earlier, the LCP has been used as a versatile medium for the biophysical and structural characterisation of membrane proteins (2020).…”

Lipid Bilayer Degradation Induced by SARS-CoV-2 Spike Protein as Revealed by Neutron Reflectometry

“…The coronavirus disease 2019 (COVID- 19) is a severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2), a spherical-shaped enveloped virion with a single positive RNA strand within the β coronavirus family [1][2][3] . As other enveloped viruses, such as the human immunodeficiency virus (HIV), influenza virus and ebola, SARS-CoV-2 exhibits in its envelope a large number of glycosylated proteins, named spike proteins or S-proteins, which are fundamental for the virus to enter the host cell 4,5 .…”

“…The natural phospholipid mixtures were characterised by a polydisperse acyl chain length composition (C16-18) and a certain level of unsaturation (1-3 double bonds) 16,17 . Given the abundance of such lipid components and cholesterol in the mammalian plasma membrane 18 , they were chosen in our study to reproduce biologically relevant models of the plasma membrane 19 .…”