Structural studies of atomic interactions in membranes: bridging the gap between physics and membrane biology

The focus of this work is observe the atomic and molecular interactions between molecules which comprise cell membranes. Cellular membranes are the gate-keepers of life. Life has evolved from single-celled organisms to more complex multi-cellular organisms partially because of the compartmentalization of cell membranes. In the last century one of the great challenges was to decode DNA - the molecular blueprint for life. In the next century one of the greatest challenges is to understand how membranes are formed and function; as they are not only everywhere but are also necessary to sustain life. Cell membranes control what can go into and out of the cell, the so-called 'molecular traffic' acting as gate-keepers. This role is important in controlling disease, disease and nutritional balance in different parts of the human body. This research proposes to look at the interactions between the molecules which make up biological membranes on the atomic scale, where one can see how individual atoms in different molecules interact with one another. This is important because it reveals the details of interactions and can inform us about how these interactions take place.

The techniques which will be used to see the atomic structure of membranes are neutron scattering techniques using the UK ISIS neutron facilities which are located at Rutherford Appleton Laboratories in Oxfordshire (UK) and managed by the UK government funded Science and Technology Facilities Council (STFC). Measurements of these molecules using neutrons shows the details of interactions between the different atoms present. Another technique which will be used is Nuclear Magnetic Resonance (NMR) which allows for different atomic aspects of the membrane to be seen. Combing this with computer models, we will be able to build a structure of the membrane which is atomically accurate.

Understanding membranes is important for a variety of reasons. First they are present in all plants and animals and indeed are one of the reasons that life exists. Understanding the structure of membranes is also needed to understand the regulation of cell activity and so this research will have a major impact on our understanding of the mechanisms of transport across the cell membrane, such as drugs and nutrients. The results of the study will aid descriptions of many of the things that membranes do, such as signal transduction - which is important in passing messages between brain cells and the body via molecules called neurotransmitters, the passage of drugs into cells and the effect of external influences on cells from toxins and antimicrobial agents.

This research, which aims to understand the physics of membranes on a molecular scale, could have several different avenues of impact. Firstly a greater understanding of cell membranes is important to drug design. There is relatively little understanding of how drugs interact in the human body on an atomic length scale, in order to design drugs that target specific cells a portion of the cell membrane, the gate-keepers for the cell, must be able to recognize the drug. Understanding the way that molecules in the membrane interact with each other and the surrounding physiological environment is a step towards understanding how a putative drug might cross the cellular membrane. This project will also look at how the molecules that make up a cell membrane interact with things like hormones and peptides cross the cell membrane. Understanding mechanisms for crossing cellular membranes can further aid in pharmaceutical drug design.

The role of hydrophobic and hydrophilic forces - that is molecules that like water (such as salt) and molecules that tend to move away from water (like oil) in membranes is not well understood, even though the play an important role in conducting traffic across the membrane. The results from this work will shed light on the complex interplay between these forces that allow membranes to function. This will aid in our fundamental understanding of not only how existing membranes function but also in how membranes are formed in the first place. Understanding these forces will also help to aid in descriptions of biological phenomena such as protein folding and aggregation of harmful peptides which are thought to cause diseases such as Alzheimer's.