Membrane transport systems

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The goal of this research is to design simple chemical systems that reproduce and improve upon the membrane transport functions found in all cellular life.  In the last decade, this program has produced a wide array of new compounds and chemical systems that have reproduced many basic functions of natural ion channels.  It is now possible to design and prepare synthetic compounds that are as active as natural examples using simplified and rapid syntheses of ion channel candidates through conventional solution and solid-phase synthesis.  The program of research proposed confronts both practical and fundamental challenges in the design and assembly of membrane transport systems.  The new syntheses have produced new classes of active compounds for mechanistic investigation and which will demonstrate new types of regulated ion transport.  In a parallel track, we have explored some examples in which ion channels have been formed through directed self-assembly of suitable components.  The channels produced are unprecedented, complex, and very challenging to study.  Whatever their structure(s), is clear now that the simple design ideas that motivated the initial effort are too naïve.  We have developed thermodynamic simulations to analyze and predict how self-assembly processes occur in homogeneous solution, and propose extensions to deal with the energetic complexities encountered in the bilayer membrane phase.  On a technical level, we continue to develop techniques to handle and inject a few thousand channel-forming molecules into bilayer membranes.   The next practical target is a stabilized and supported bilayer membrane initially for our own use in the characterization of new transporters.  To the extent that this is successful, sensor applications will be possible.