Self Assembly of Biological Lipids and of Polymers

University Of Washington, Seattle WA

Investigators

Abstract

This theoretical project will study several important biological problems utilizing powerful methods from polymer physics. This is possible because the hydrocarbon chains of biological lipids, which make up all membranes within the body, are short chain polymers. One such problem is the study of "rafts," high density islands of sphingolipids and cholesterol in the phospholipid sea; islands which attract, inter alia, signalling proteins. Although there is unusual excitement about this phenomena, as it requires significant revision of the standard view of membranes, there is little molecular theory on the unusual ordered fluid phase typical of the raft. This is a phase in which the chains have fewer gauche bonds than the normal liquid crystal phase, yet is without the translational order characteristic of the gel phase. Several methods, including self-consistent field theory, will be utilized along with a realistic description of the lipid chains to understand the factors which encourage, or inhibit, the formation of rafts. A second problem of great importance is that of membrane fusion, a process necessary for viral infection, fertilization, and most intra-cell trafficking. The process is not understood. This group has carried out simulations of this process utilizing models which have proved of great use in the study of polymers. These simulations reveal a very different fusion mechanism than that commonly accepted. These studies will continue in order to elucidate the pathway which is followed during fusion. The potential impact is great given the connection between fusion and infection, and fusion and fertilization. Another project of note is that concerning the study of crystallization of membrane proteins. The structure of these important proteins is not known, in general, as most of them have not been crystallized, a prerequesite for x-ray analysis. Rather recently crystallization of such proteins was accomplished using cubic lipid phases. Why such unusual phases should bring about crystals of proteins is not understood. This problem fits well with the techniques used by this group, which successfully predicted the existence, and non-existence, of various bicontinuous cubic phases in block copoloymers, and have extended these techniques to include interaction between lipid membranes and proteins. If the basic principles underlying this process can be understood, it could lead to an increase in the number of such proteins whose structure can be analyzed. %%% This theoretical project will study several important biological problems utilizing powerful methods from polymer physics. This is possible because the hydrocarbon chains of biological lipids, which make up all membranes within the body, are short chain polymers. The projects studied illustrate the great potential of bringing methods of polymer physics to bear upon important problems in the biological sciences. ***