Prof. Brown was born in Los Angeles, California. He received the A.B. degree in 1970 from the University of California at Santa Cruz. While an undergraduate, he conducted research in nuclear magnetic resonance (NMR) spectroscopy at the Laboratory of Chemical Biodynamics at Berkeley, and continued this during his doctoral studies at Santa Cruz. He received a Ph.D. degree in 1975.
Brown was awarded a postdoctoral fellowship from the U.S. National Institutes of Health (NIH) to conduct research in Europe. He spent three years working with Joachim Seelig at the Biozentrum of the University of Basel in Switzerland, and with Ulrich Häberlen at the Max Planck Institute in Heidelberg, Germany. Brown then joined the laboratory of Wayne Hubbell in the Department of Chemistry of the University of California at Berkeley.
In 1980 Brown became an Assistant Professor at the University of Virginia. He received a Sloan Fellowship and a NIH Research Career Development Award, and was promoted to Associate Professor with tenure in 1985. In 1987 he joined the faculty of the University of Arizona as Full Professor in the Department of Chemistry and Biochemistry, along with a joint appointment in the Department of Physics. He is a member of the Committee on Neuroscience and the Applied Mathematics Program. He has been a Visiting Professor at the University of Lund, Sweden, the University of Würzburg, Germany, the University of Florence, Italy, and Osaka University, Japan.
Notably Brown was a pioneer in developing the use of deuterium (2H) NMR spectroscopy for measuring the order parameters and relaxation times of biomolecules. This method has since become one of the mainstays of biophysical chemistry. He developed new solid-state NMR approaches to unveil the emergence of membrane elasticity over nano- and mesoscopic length scales. Additional NMR methods have been implemented to study the structural dynamics of membrane proteins. Michael Brown has put forth a new Flexible Surface Model (FSM) that effectively supersedes the standard fluid mosaic model found in textbooks. His innovation of a two-way coupling of lipids and proteins explains membrane protein function by nonspecific material properties of lipid bilayers. The spontaneous monolayer curvature competes with the solvation energy of the proteolipid interface, and explains lipid modulation of the conformational energetics of membrane proteins. The membrane curvature stress field is linked to key biomembrane functions involving G-protein–coupled receptors (GPCRs) and ion channels. For G-protein–coupled receptors such as rhodopsin—as well as membrane transporters and ion channels—Brown's flexible surface model illuminates how the properties of biomembranes underlie key cellular functions, with potential implications for drug discovery and human medicine.
(1) For membrane lipids, Brown pioneered the development of solid-state NMR methods (order parameter analysis, relaxation methods) in the first detailed studies of lipid structure, ordering, and dynamics. His original implementation of solid-state NMR relaxation methods led to seminal concepts of collective membrane phenomena involving elastic properties that emerge over mesoscopic length scales. Moreover, he extended these concepts to illuminate the roles of polyunsaturated lipids in biological signaling at the membrane level. His innovation (together with Prof. Joachim Seelig) of using solid-state deuterium NMR spectroscopy for investigating the structure and dynamics of liquid-crystalline molecules, including membrane lipids and membrane proteins, has had a substantial impact on the field of biophysical chemistry.
(2) Brown's experimental measurements of the magnetic field dependence of the NMR relaxation rates of liquid-crystalline systems have played a crucial role in the refinement of force fields for molecular dynamics (MD) simulations of membrane constituents. He was the first to develop a comprehensive theoretical basis of the nuclear spin relaxation of biomolecules in terms of motional mean-square amplitudes (order parameters) as well as rates of structural fluctuations. For lipid bilayers, the new model relates the energy landscape of the molecular fluctuations to the emergence of elastic properties. A membrane deformation model was proposed to establish the energy landscape in terms of viscoelastic properties that emerge on the mesoscopic length scale of the stochastic bilayer fluctuations. The combined order parameter and relaxation measurements give unique knowledge of the structural fluctuations for membrane lipids and membrane proteins. This work has had a substantial impact, and is very well cited and highly regarded in the field.
(3) Brown's work in the area of membrane lipid-protein interactions he has produced a new vision that significantly advances the field of biomembranes. He was the first to firmly establish how membrane lipids govern the energetics of membrane proteins, and he developed a new biomembrane model. His innovation of a two-way coupling of lipids and proteins explains membrane protein function by nonspecific material properties of lipid bilayers. The new biomembrane model for lipid-protein and lipid-peptide interactions is based on differential geometry using the Helfrich free energy. According to the Flexible Surface Model, elastic deformation of the membrane bilayer is coupled to the conformational energetics of membrane proteins, including receptors and ion channels. Frustration of the intrinsic curvature of the bilayer is linked to allosteric regulation of membrane proteins that are implicated in key signaling or transport functions.
(4) Most recently, Brown has applied his methods to membrane bilayers containing the G-protein–coupled receptor (GPCR) rhodopsin. He determined the solid-state NMR structure of the retinal ligand of rhodopsin, and the changes upon light activation in the visual process. He established how local motions of bound cofactors initiate the activation of membrane receptors in a membrane lipid environment. Brown showed for the first time how light-induced changes in the local dynamics of the retinal ligand stimulate large-scale activating fluctuations of rhodopsin. He proposed and critically tested a multiscale mechanism, whereby retinal triggers collective helical fluctuations in the activated state. He introduced the concept of a dynamically activated receptor as described by an ensemble activation model. His work illuminates how the properties of biomembranes underlie key cellular functions with potential with clear implications for human medicine and drug discovery.
Michael Brown's accomplishments have been recognized through the award of Fellowships from the Alfred P. Sloan Foundation, the Japanese Foundation for the Promotion of Science, the Fulbright Program, the American Physical Society (APS), the Biophysical Society, the Galileo Circle, and the American Association for the Advancement of Science (AAAS). Among his accolades he was appointed Röntgen Professor of Physics at the University of Würzburg in Germany and delivered the Wilhelm Conrad Röntgen Lecture. Most recently he received the Avanti Award in Lipids from the Biophysical Society.