Microfluidic Devices in Chemical Biology / a new frontier in the study of biological membranes

Lead Research Organisation: Imperial College London
Department Name: Dept of Chemistry

Abstract

There are many questions still to be answered in biology and the life sciences and sometimes it is necessary to take a new approach to how this is done. One way is to use techniques from the physical sciences, such as chemistry and physics and apply them in a novel way to biology. This project aims to use a well understood physical science technique in order to further the understanding of a key biological problem. Biological membranes are complex, environments which provide a barrier between the inside and outside of the cell. The membrane is made of a wide range of molecules known as lipids which sit top to tail in an arrangement called a bilayer. Each lipid present in the bilayer fulfils a specific purpose. Also present within the membrane are molecules known as membrane proteins, which allow there to be transport of signals and nutrients between inside and outside of the cell. Membrane proteins are hydrophobic ('water hating') and need to be surrounded by lipids (which have a hydrophobic body which protects the protein) to function. Little is understood about the interplay between the lipids that make up the membrane and the proteins they surround. The complexity of the lipid membrane also makes it very difficult to study. One way to combat this problem is to make synthetic membranes to simplify the environment which the protein is embedded in. However a further problem is that membrane proteins are extremely difficult to work with and can only be obtained in minute quantities. A solution to both of these problems would be to use a technique known as microfluidics. A microfluidic device is a way to provide a reproducible controllable method to make synthetic lipid bilayers that can then be used to study membrane proteins. Samples flow down small channels (usually less than 1mm wide) with a constant smooth flow. The advantages are that small volumes, such as is required for working with membrane proteins are used and we can control the way that the membrane protein is mixed with the lipid environment. In this project, microfluidic devices will be used to study how membrane proteins interact with synthetic lipid bilayers. A microfluidic device will be designed and made and mixtures of lipids, mixed with fluorescent dyes, will be deposited in a bilayer on the patterned glass surface. This will act like the cell membrane. Once the way in which the lipids are deposited is established, helical peptides - molecules which mimic the region of membrane proteins that sits in the lipid bilayer will be added. These peptides will have fluorescent labels attached to allow them to be seen and analysed when they interact with the lipids. By changing the conditions under which these peptides are introduced, more can be understood about the way they interact with the lipid bilayers. Once this has been achieved, actual membrane proteins can be introduced to try to understand the way that these proteins enter cell membranes and achieve the shape that they need to be in to be able to function. Natural properties of the proteins and how they behave will be used to analyse how well the proteins have incorporated into the lipid layer and whether they are functioning correctly. Finally the project will take what we have learnt about introducing membrane proteins into lipid bilayers and use these techniques in order to fabricate new materials. These will be made by taking the protein, embedded in its lipid bilayer and adding in materials known as ceramics in order to make the lipid-protein 'film' more easy to handle. Alternatively very small metal particles known as nanoparticles can be attached to the proteins in the bilayer. Due to their size, these have interesting properties and incorporating them in an ordered lipid array attached to proteins opens up the possibility of new and interesting biomaterials.

Publications

10 25 50