Dr. Anne Hinderliter, Professor

Biophysical Chemistry

Office: SSB 152B
Phone: (218) 726–7062
Fax: (218) 726–7394
E-mail: ahinderl@d.umn.edu

• Ph.D. 1994, Cornell University

Research Interests

Signaling at the Membrane

Membranes offer infinite possible docking combinations onto which to assemble proteins dedicated to a specific signaling outcome. Little appreciated is the very act of 'docking' the underlying pattern of membrane to which the molecule docked will be altered. Membranes are a self-organized system with unique biological properties. To understand membrane localized docking interactions, a strong research program that has an emphasis in binding interactions, of how to measure experimentally and model binding, is critical. My work has a common theme of having predictive power in the how and why things bind and has an emphasis in interactions localized on or near the membrane. This body of work has evolved in the past few years from elucidating how signal transduction complexes may be formed at the membrane to applying these defined principles to systems of pharmacological and material science interest. My long-term goal is to define those interactions that both lead to pathological interactions at the membrane, and to use such understanding to formulate unique organized systems mimicking these interactions to both treat and diagnose disease states.

Why would I have such an interest in membrane-localized phenomena? The membrane is more than a barrier to drug delivery, it has still little understood properties that can transmute and modify the influence of drugs, signaling molecules, and proteins. In eukaryotes, a plethora of lipid species exists, with small differences in lipid chemical structure. The synthesis of such a variety of lipids argues against a simple barrier function for cellular membranes. We have suggested (Almeida et al., 2005; Hinderliter et al., 2004; Hinderliter et al., 2001) that the role of lipids is that of signal amplification through multiple nearest neighbor interactions and of regulation of assembly of signaling complexes. Lipids have weak nearest neighbor interactions offering a readily malleable surface that protein or drug may rework to alter the propensity of signaling molecules to co-cluster with lipid domains (rafts).

Small changes in lipid chemical structure such as increasing the length of an acyl chain by a methylene group, changes the small cooperative interactions that exists between lipids. A favorable interaction of a protein with certain lipids induces accumulation of those lipids in the neighborhood of the protein. Through nearest neighbor interactions between lipids, these small changes ripple outward. The change in local composition of lipids is sensed by other proteins, which are recruited to the domain and will induce further reshuffling. Both aspects of the question, protein and lipid chemical structure and how one influences the other, must be well developed to fully test the hypothesis.

Representative Publications

Education

• Ph.D. 1994, Cornell University