Interdisciplinary Initiatives Program Round 3 – 2006

Steven Boxer, Chemistry
Nick Melosh, Materials Science & Engineering

It is estimated that 1/3 of all proteins in the human genome are membrane proteins. Membrane proteins are the gatekeepers of the lipid bilayer membranes that surround and define cells and organelles, e.g., the nucleus, mitochondria, etc. Ion channels are a particularly important class of membrane proteins that serve as cellular transistors, allowing passage of large number of ions in response to binding events and/or transmembrane potential. The process of gating charge passage involves a structural change that has been the subject of much debate. We propose to develop a device that combines optics and electrophysiological measurements so that these structural changes can be characterized with very high precision in an environment that is close to that of a natural cell membrane. To achieve this, we will combine expertise in membrane assembly and optical interferometry from the Boxer lab in Chemistry with state-of-the-art fabrication methods developed in the Melosh lab in Material Science. The device we propose allows simultaneous measurements of ion channel gating by a type of optical interferometry, which can provide sub-nm position information, with high sensitivity electrical measurements, which characterize the passage of ions through the channel. If successful, this type of device could be broadly useful for studies of membrane proteins and more complex assemblies.