Matthew A. Holden
Assistant Professor of Chemistry, University of Massachusetts, Amherst
Ph.D.: Texas A & M, 2004 Postdoctoral Training: Oxford University
We reconstruct cell membranes from natural and synthetic molecular components. These lipid bilayers provide a general bio-architecture that can be precisely tuned to study a variety of biological problems. We focus on the study of ion channels, transporters and other membrane-penetrating species. In addition, bilayer networks enable the creation of biological mimics whose functions are based on the type of membrane proteins incorporated into the network. 1. Bionetworks Droplets immersed in an oil/lipid mixture become encased in a lipid monolayer. When two such droplets are contacted, a droplet-interface bilayer (DIB) is formed; many connected droplets comprise a bionetwork. By incorporating membrane proteins such as ion channels and pumps into DIBs, bionetworks can be engineered to carry out specific functions. Using this approach, we build stimulus responsive bionetworks in order to model electrically driven systems such as heart and nerve tissues. 2. Membrane Transport The trafficking of molecules across cell membranes is of central interest in metabolism and disease. Assays of membrane transport using live cells are performed under stringent conditions in order to maintain cell viability. Using arrays of DIBs, we study the transport of molecules from one droplet to another, maintaining the conservation of mass throughout the assay. Both passive transport (diffusion of molecules across the bilayer) and active transport (membrane transporters using energy to drive transport) are investigated. 3. Single Ion Channel Investigation The incorporation of functional ion channels into artificially formed lipid bilayers is a challenging task. Many species of ion channel are delicate and quickly denature or otherwise lose activity when purified from their native systems. Using a mechanical probe, we transfer membrane proteins (such as ion channels) directly from cellular systems to preformed bilayers for single-channel investigation by electrophysiology. Automation of the transfer technique represents a key advancement in the study of ion channels.