Michael F Brown
Professor, Applied Mathematics - GIDP
Professor, BIO5 Institute
Professor, Chemistry and Biochemistry-Sci
Primary Department
(520) 621-2163
Research Interest
Michael F. Brown is Professor of Chemistry & Biochemistry at the University of Arizona. He is co-director of the Biological Physics Program and the Chemical Physics Program, and was a co-founder of the Biological Chemistry Program at the University of Arizona. He is internationally renowned for his work on the molecular basis of activation of G-protein-coupled receptors that are the targets for the majority of pharmaceuticals and medicines used by humans. The focus of his work is on biomembranes, with a particular emphasis on lipid-protein interactions in relation to potential drug targets involving membrane proteins. He is involved with investigation of the molecular basis of visual signaling involving rhodopsin. Moreover, Professor Brown is an expert in nuclear magnetic resonance (NMR) spectroscopy. His activities in the area of biomolecular NMR spectroscopy involve the devolvement and application of methods for studying the structure and dynamics of biomolecules. Michael Brown has authored over 130 original research papers, 10 book chapters, 4 book reviews, and has published more than 275 abstracts. His current H-index is 43. He numbers among his coworkers various prominent scientists worldwide. He presents his work frequently at national and international conferences, and is the recipient of a number of major awards. Professor Brown's many contributions have established him as a major voice in the area of biomembrane research and biomolecular spectroscopy. He is frequently a member of various review panels and exerts an influence on science policy at the national level. Among his accolades, he is an elected Fellow of the American Association for the Advancement of Science; American Physical Society; Japan Society for the Promotion of Science; and the Biophysical Society. He is a Fellow of the Galileo Circle of the University of Arizona. Most recently, he received the Avanti Award of the Biophysical Society. This premier honor recognizes his vast and innovative contributions to the field of membrane biophysics, and groundbreaking work in the development of NMR techniques to characterize lipid structure and dynamics. Most recently he presented the 2014 Avanti lecture of the Biophysical Society.

Publications

Brown, M. F., & Molugu, T. R. (2016). Cholesterol-Induced Suppression of Membrane Elastic Fluctuations at the Atomistic Level. Chemistry and Physics of Lipids, 199, 39-51.
Williams, G. D., Beach, J. M., Dodd, S. W., & Brown, M. F. (1985). Dependence of deuterium spin-lattice relaxation rates of multilamellar phospholipid dispersions on orientational order. Journal of the American Chemical Society, 107(24), 6868-6873.

Abstract:

2H NMR studies of a homologous series of 1,2-diacyl-sn-glycero-3-phosphocholines with perdeuterated saturated chains, ranging in length from C12:0 to C16:0, have been performed with use of quadrupolar echo techniques at a resonance frequency of 55.4 MHz. Randomly oriented, multilamellar dispersions containing 50 wt % H2O in the liquid crystalline (Lα) phase have been employed. The 2H spin-lattice relaxation times (T1) and C-2H bond segmental order parameters (SCD) of each of the resolved quadrupolar splittings have been obtained from the powder-type spectra, corresponding to a random distribution of orientations, as well as from the 0°C oriented subspectra obtained by numerical deconvolution (de-Pakeing). Evidence that the spin-lattice relaxation rate profiles as a function of chain position T1-1(i) are related to the corresponding order profiles SCD(i) by a square-law functional dependence has been obtained, indicative of a contribution from relatively slow fluctuations in the local bilayer ordering to the relaxation. The results suggest that two broad classes of motions influence the 2H spin-lattice relaxation rates of lipid bilayers: rapid local motions, most likely due to bond rotational isomerizations and long-axis rotational diffusion of the lipid chains, as well as slower director fluctuations as found in other liquid crystalline mesophases. © 1985 American Chemical Society.

Brown, M. F. (1983). Unified picture for spin-lattice relaxation of lipid bilayers and biomembranes. The Journal of Chemical Physics, 80(6), 2832-2836.

Abstract:

The present study compares and interprets the 1H, 2H, and 13C spin-lattice (T1) relaxation times of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), in the liquid crystalline phase, in terms of models for the molecular dynamics of lipid bilayers. The 1H T1 times of the DPPC bilayer hydrocarbon region at two frequencies and 13C T1 data at seven frequencies, for which the relaxation is dipolar in origin, as well as the 2H T 1 data at three frequencies, due to the quadrupolar interaction, can be unified and interpreted in terms of a collective model for order fluctuations. In normalizing the 13C T1 data to the 1H and 2H T1 values, a vibrationally corrected 13C-1H distance parameter of rCH0=1.14 Å has been assumed, rather than the equilibrium bond length of 1.09 Å. The analysis suggests that the behavior of the individual acyl chain segments of lipid bilayers, in the liquid crystalline phase, is similar to that of molecules in nematic fluids. © 1984 American Institute of Physics.

Subramaniam, V., D'Ambruoso, G. D., Hall Jr., H. K., Wysocki Jr., R. J., Brown, M. F., & Saavedra, S. S. (2008). Reconstitution of rhodopsin into polymerizable planar supported lipid bilayers: Influence of dienoyl monomer structure on photoactivation. Langmuir, 24(19), 11067-11075.

PMID: 18759470;PMCID: PMC2726791;Abstract:

G-protein-coupled receptors (GPCRs) play key roles in cellular signal transduction and many are pharmacologically important targets for drug discovery. GPCRs can be reconstituted in planar supported lipid bilayers (PSLBs) with retention of activity, which has led to development of GPCR-based biosensors and biochips. However, PSLBs composed of natural lipids lack the high stability desired for many technological applications. One strategy is to use synthetic lipid monomers that can be polymerized to form robust bilayers. A key question is how lipid polymerization affects GPCR structure and activity. Here we have investigated the photochemical activity of bovine rhodopsin (Rhô), a model GPCR, reconstituted into PSLBs composed of lipids having one or two polymerizable dienoyl moieties located in different regions of the acyl chains. Plasmon waveguide resonance spectroscopy was used to compare the degree of Rho photoactivation in fluid and poly(lipid) PSLBs. The position of the dienoyl moiety was found to have a significant effect: polymerization near the glycerol backbone significantly attenuates Rho activity whereas polymerization near the acyl chain termini does not. Differences in cross-link density near the acyl chain termini also do not affect Rho activity. In unpolymerized PSLBs, an equimolar mixture of phosphatidylethanolamine and phosphatidylcholine (PC) lipids enhances activity relative to pure PC; however after polymerization, the enhancement is eliminated which is attributed to stabilization of the membrane lamellar phase. These results should provide guidance for the design of robust lipid bilayers functionalized with transmembrane proteins for use in membrane-based biochips and biosensors. © 2008 American Chemical Society.

Weerasinghe, N., Fried, S. D., Perera, S. M., Eitel, A. R., Chawla, U., Molugu, T. R., Struts, A. V., & Brown, M. F. (2017). G-Protein-Coupled Receptor Activation through Membrane Deformation. Biophysical Journal.