Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Current Topics - Cutting-Edge Studies Using Artificial Membranes
Foreword
Naohide Hirashima
Author information
JOURNAL FREE ACCESS FULL-TEXT HTML

2018 Volume 41 Issue 3 Pages 287

Details

Biomembranes, such as the plasma membrane, play essential roles in biological systems. The plasma membrane defines the cell boundary and works as an interface between cytosol and the extracellular environment. A variety of receptors are expressed on the plasma membrane, and these transmit extracellular signals to the intracellular signal transduction system. In addition, various substances are transported bidirectionally through the plasma membrane.

To understand the roles and mechanisms of biomembranes, artificial membrane systems such as liposomes and planar lipid bilayers have been developed. Furthermore, liposomes are used as drug delivery systems both in the process of drug development. Together with recent advances in experimental techniques, however, many researchers in fields other than the life sciences now use artificial membrane systems to construct unique experimental systems. This Current Topics focuses on recent studies using artificial membrane systems by three scientists with different backgrounds.

Liposomes have been used in various ways not only to understand the mechanisms of biological phenomena but also to construct artificial cell systems that mimic cellular shape, movement and physiological function. From a structural point of view, liposomes are divided into three categories: small unilamellar vesicles (SUV), large unilamellar vesicles (LUV) and multilamellar vesicles (MLV). In general, their size is smaller than real cells (about 10 µm in diameter). Recently, new methods for preparing cell-sized giant unilamellar liposomes have been developed, and we can use such giant liposomes as comparable to real cells. Numerous reports on artificial cells using cell-sized liposomes have been published. One example involves the expression of green fluorescence protein from DNA in a liposome.

The first review, by Takiguchi (biophysics), deals with the study of cell-sized giant liposomes that contain a cytoskeleton inside the vesicles. Takiguchi et al. succeeded in observing reversible morphological changes in liposomes that encapsulate microtubules. Their results contribute to the possibility of developing an artificially motile cell mode (robotics), and thus to constructing a smart drug delivery system in the future.

As mentioned above, the plasma membrane works as an interface between the intra- and extra-cellular environment. The plasma membrane contains many membrane proteins such as receptors, ion channels and transporters. It is very intriguing to construct artificial proteins that mimic the function of membrane proteins. The artificial membrane is a good experimental system in which to evaluate the function of the membrane protein molecules; because components of the membrane can be defined precisely and correctly in the artificial membrane, unknown factors are excluded.

The second review, by Muraoka (organic synthetic chemistry), describes the synthesis of such functional molecules, and evaluates their activity using artificial membrane systems. A multi-pass transmembrane (MTM) structure is prevalent in membrane proteins. For example, many ion channels feature a common structure of membrane-spanning α-helices connected with flexible loop chains. Muraoka designed and synthesized molecules that have a hydrophobic domain as the membrane-spanning domain and a hydrophilic unit as the extra-membranous loop part. The electro-physiological properties of these synthesized ion channels were evaluated using a planar lipid bilayer system. Furthermore, Muraoka succeeded in developing an ion channel-like molecule that behaves like a ligand gated ion channel activated by phenethylamine.

The third review, by Oiki (physiology), surveys experimental systems in which artificial membrane systems are utilized to investigate ion channel activity, including liposomes, lipid bilayers and nanodiscs. Oiki and Iwamoto developed a new bilayer system called the ‘contact bubble bilayer’ (CBB). In this method, two water bubbles form in a bulk oil phase in which lipids are dissolved and come into contact with each other by glass pipettes with an Ag/AgCl electrode to form a lipid bilayer. Using this system, it is possible to carry out normal electrophysiological measurements, but with higher resolution due to the lower electrical background noise and application of a higher membrane potential. It is possible to perfuse this aqueous solution; however, this system also allows us to perfuse the “membrane” interior quickly by applying hydrophobic substances with a pipette placed near the CBB. Using this perfusion technique, the immediate effects of cholesterol in the lipid bilayer on the activity of the potassium channel are described.

I hope that these reviews help readers understand today’s cutting-edge research using artificial membranes, and provide hints and impetus for creative new experiments and collaboration among researchers from different fields.

 
© 2018 The Pharmaceutical Society of Japan
feedback
Top