Yeast cell surface is not only a boundary that separates the self from others by confining the necessary components for life support, but also an important interface to interact with the external environment and others. Therefore, if the functionality of the cell surface can be manipulated to design interactions with the extracellular environment, yeast cells will be able to be utilized in various fields such as material production and medicine. This review provides an overview of cell surface engineering technology, a promising tool for manipulating the functionality of the yeast cell surface, its applications in various fields, and recent research on its improvement.

Cells are composed of a lipid bilayer membrane that separates the cell from the outside world. In order to modify the cell, it is necessary to access the inner space of cell, in other words, the cytoplasm by some means. Although physical or mechanical penetration of the cell membrane is one of the potential methods, an approach based on a well understanding of the nature of the cell membrane is necessary. We have developed our original device, nanoneedles with a diameter of 200 nm, and have clarified in detail the method and conditions for efficient insertion into animal and human cells.

When membrane curvature or stretch is induced by extracellular or intracellular factors, the spacing between lipid heads should widen and the hydrophobic core region of the membrane should become more exposed to the membrane surface. By focusing on the interaction of this hydrophobic core with appropriate amphiphilic molecules, a unique method of membrane structural transformation and its application are expected. In this paper, we would like to consider the interaction mode of peptides with the cell membrane upon membrane structural transformation from the viewpoint of intracellular delivery applications, using octaarginine and L17E peptides developed in our laboratory as examples.

Biomolecules such as proteins or nucleic acids have been utilized as biopharmaceutical drugs, which produce various pharmacological activities. The development of a novel transdermal delivery system of biopharmaceuticals attracts much attention because it provides the easy and safe administration method compared to injection. The Solid-in-Oil (S/O) nanodispersion technique consists of the oil-based dispersion, in which the biopharmaceuticals are coated with hydrophobic surfactant molecules and dispersed in the oil phase as nanometer-sized particles. Insulin, a model pharmaceutical drug, enables to be dispersed in isopropyl myristate (IPM), that is known to be an effective skin penetration enhancer, by forming the S/O nanodispersion. The permeability of insulin into the skin was drastically enhanced. Further, the transdermal vaccination has been studied as one of the most important applications of the S/O nanodispersion. It was proved that the S/O nanodispersion containig a model antigen produced the antigen-specific antibodies and induced the cytotoxic cellular immunity in mouse. These results suggested that the S/O nanodispersion technique is useful for delivering biopharmaceuticals into the skin, and expected to become available in clinical.