(Invited) Integrated Model System of the Biological Membrane on Solid Surface
Authors: Morigaki Kenichi 
Published: December 2024

The biological membrane comprising lipid bilayer membrane and membrane-associated proteins performs a wide range of cellular functions, including signal transduction and energy conversion. Diseases such as cancer and COVID-19 are mechanistically linked with the biological membrane. An important structural feature of the biological membrane is the combination of two-dimensional (2D) and three-dimensional (3D) architectures that form organized 2D fluid and create compartments in the cell and cell-cell junctions. The dynamic self-assembly of the 2D/ 3D membrane structures and their cooperative functions are important in understanding the biological membranes.

Synthetic model membranes such as lipid vesicles and black lipid membrane (BLM) have played important roles in extending our understanding of the biological membrane. They also provide platforms for biosensors and biomedical applications. Substrate supported lipid bilayers (SLBs) are a model membrane supported on a planar solid substrate such as silicon and glass (1). They have some unique features compared with other formats of model membranes. First, they are mechanical stable owing to the solid support. Second, they are accessibility to highly sensitive analytical techniques at the liquid-solid interface. Third, they are amenable to application of micro-fabrication techniques. These features render SLBs highly attractive for the development of devices that utilize artificially mimicked cellular functions.

We have been developing an integrated model system of the biological membrane on the solid substrate utilizing a micro-patterned membrane of polymeric and natural lipid bilayers (2). The polymeric bilayer is formed from polymerizable diacetylene-containing phospholipid (DiynePC) and acts as a framework to support embedded lipid membranes. The embedded natural lipid membranes retain important characteristics of the biological membrane such as fluidity, and are used as a model system that reproduces the functions of the biological membrane. Various types of natural lipid membranes and proteins have been incorporated. We incorporated rhodopsin photoreceptor (Rh), a G-protein coupled receptor (GPCR), and its cognate G-protein transducin (Gt) into the patterned model membrane. The 2D diffusion and distribution of Rh and Gt were studied for elucidating the functional roles of lipid membrane environments (3). We also reconstituted natural membranes directly from their sources such as mammalian cell membranes and plant thylakoid membranes (4). Reconstituted thylakoid membrane provides a platform for investigating the functional roles of 2D membrane organizations in the photosynthesis.

The 3D compartments formed by the biological membrane are also important for cellular functions. For mimicking the 3D compartments, we have developed a nanometric gap structure on the patterned membrane by attaching the polymeric bilayer with a silicone elastomer (PDMS) using an adhesion layer having a defined thickness (nanogap-junction) (5). Nanogap-junction provides a unique possibility to analyze biological molecules with a vastly heightened signal-noise ratio. Nanogap-junction can be used as a platform to study molecular properties and functions of membrane proteins. It should also provide opportunities to detect biomarker molecules using sandwich immuno-assay on the fluid membrane. The combination of 2D mobility and 3D compartmentalization of the membrane will be exploited to open new possibilities in the biomedical applications.

The integrated model membrane reproduces some essential structural, physicochemical, and functional features of the biological membrane. These solid supported model membranes have been mainly studied by the optical methods. However, they should be integrated with electrodes, enabling electrochemical detection of the membrane functions. In combination with advanced fabrication technologies and analytical methods, it should provide novel opportunities in fundamental biological sciences as well as biomedical/ analytical applications such as "single molecule diagnostics".

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