**Abstract**

Red cells are full of unique biological properties such as immune evasion and molecular-specific permeability. These properties originate from various membrane proteins on the surface of the cell membrane. For this reason, red cell membrane is coated on nanomaterials or sensors to bestow the functionalities of the membrane proteins. In this chapter, various types of membrane proteins of red cell and its functions are described. Also, the following two experimental procedures are summarized: (I) the extraction of red cell membrane containing membrane proteins and (II) coating of the extracted cell membrane onto the nanoparticles and solid surface of sensors. Finally, the applications of red cell membrane in drug delivery system and biosensor are discussed.

**Keywords:** red cell membrane, membrane proteins, cell membrane coating, biosensors

## **1. Introduction**

Red cells (RCs), also called as erythrocyte, are the most abundant cells in the body and highly specialized in gas transportation [1]. RCs deliver oxygen from the lungs to all body tissues and carry carbon dioxide to the lungs. For the delivery of the gases, RCs circulate through blood vessels to the whole body without being trapped inside narrow capillary vessels (5–10 μm in diameter) which are smaller than the size of RCs [2]. Also, RCs do not get attacked by immune system such as mononuclear phagocytic system (MPS) and complement system (CS) [3, 4]. The unique characteristics of the RCs come from specialized microstructure of RC. The microstructure of RC has a biconcave disc-like shape and is fully packed with hemoglobin instead of nucleus and intracellular organelles. Also, various membrane proteins and carbohydrates are embedded in the cell membrane which characterizes intrinsic functionalities of RCs [5]. The biconcave disc-like shape maximizes the surface area of the cell, which increases the gas exchanges between internal and external gases. Hemoglobins are oxygen-transport metalloproteins that bind gases such as oxygen and carbon dioxide. Especially, membrane proteins of RC are responsible for numerous characteristics such as permeability to specific molecules (e.g., glucose, urea, and gases), immune evasive properties, unique biconcave disc-like structure, flexibility, and deformability [4, 6]. Recently, it is reported that membrane proteins of RC can be utilized by manipulating the cell membrane [7]. The RC membrane (RCM) inside the whole blood of mice or human contains membrane proteins, which were extracted and purified. Accordingly, intriguing

researches were conducted together. For example, just like RC does, RCM-coated nanoparticles showed long circulation in the blood by evading immune responses such as MPS and CS [7, 8]. Also, RCM-coated glucose sensors showed high permselectivity to glucose [9]. As a result, the sensor was barely affected by interfering molecules such as saccharides and antioxidants. Likewise, the utilization of the functionalities of membrane protein of RC advances nanobiotechnology in the field of drug delivery system and biosensor. In this chapter, we investigate the various membrane proteins expressed on RC and its functionalities. The techniques for extraction and functionalization of cell membrane have been researched. Also, we discuss about the application of RCM functionalization for the last decade.
