Abstract

The importance of cell membranes in biological systems has prompted the development of model membrane platforms that recapitulate fundamental aspects of membrane biology, especially the lipid bilayer environment. Tethered lipid bilayers represent one of the most promising classes of model membranes and are based on the immobilization of a planar lipid bilayer on a solid support that enables characterization by a wide range of surface-sensitive analytical techniques. Moreover, as the result of molecular engineering inspired by biology, tethered bilayers are increasingly able to mimic fundamental properties of natural cell membranes, including fluidity, electrical sealing and hosting transmembrane proteins. At the same time, new methods have been employed to improve the durability of tethered bilayers, with shelf-lives now reaching the order of weeks and months. Taken together, the capabilities of tethered lipid bilayers have opened the door to biotechnology applications in healthcare, environmental monitoring and energy storage. In this review, several examples of such applications are presented. Beyond the particulars of each example, the focus of this review is on the emerging design and characterization strategies that made these applications possible. By drawing connections between these strategies and promising research results, future opportunities for tethered lipid bilayers within the biotechnology field are discussed.

Highlights

  • From hosting transmembrane proteins involved in signal transduction pathways to regulating what enters and exits a cell, phospholipid membranes represent a critically important interface within biological systems [1,2,3,4]

  • The rest of this review introduces several examples of emerging capabilities within the tethered lipid bilayer field

  • With each example highlighting a particular component of tethered lipid bilayers, such as characterization methods or ion channel engineering, the collective picture generated from these examples provides a framework to understand how tethered bilayers are moving closer to becoming widespread in various technologies

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Summary

Introduction

From hosting transmembrane proteins involved in signal transduction pathways to regulating what enters and exits a cell, phospholipid membranes represent a critically important interface within biological systems [1,2,3,4]. The hybrid bilayer has many useful properties and provides the general framework for the tethered bilayer field, there is no aqueous layer between the lower leaflet of the bilayer and the metal surface This technical limitation has prompted the development of tethered bilayers with spacer regions between the lower leaflet of the bilayer and the solid support. The lipid bilayer is not itself tethered, but rather supported upon the tethered layer, and this design limits the ruggedness of the model membrane Such bilayers do not have sufficient electrical sealing properties for quantitative characterization of ion channel activities. The functionalized substrate presents a hydrophobic surface that promotes the fusion of lipid vesicles to form a tethered lipid bilayer In this case, the spacer function of the thiolipid separates the lower leaflet of the bilayer from the solid support to enable functional reconstitution of membrane-associated proteins. With each example highlighting a particular component of tethered lipid bilayers, such as characterization methods or ion channel engineering, the collective picture generated from these examples provides a framework to understand how tethered bilayers are moving closer to becoming widespread in various technologies

Characterization Methods
Functional Analysis of Membrane-Associated Peptides
Functional Analysis of Membrane-Associated Proteins
Influenza Virus Detection
Stochastic Sensor Arrays
Air-Stable Bilayers
Findings
Perspectives
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