Michael F Brown

Michael F Brown

Professor, Chemistry and Biochemistry-Sci
Professor, Applied Mathematics - GIDP
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(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., & Williams, G. D. (1985). Membrane NMR: a dynamic research area. Journal of Biochemical and Biophysical Methods, 11(2-3), 71-81.

PMID: 3897353;Abstract:

Recent NMR relaxation studies of lipid bilayers and biomembranes are explained and briefly discussed. The results of both 2H and 13C NMR investigations suggest that, in addition to rapid local fluctuations of the hydrocarbon chains, slower, more collective motions of the bilayer exist. When the influence of the latter is recognized and properly accounted for, the contribution from local motions can be used to estimate a value for the microviscosity of the bilayer which corresponds to that of a simple n-paraffinic liquid. In general, the dynamic behavior of lipid bilayers as studied by NMR appears quite similar to that of simpler liquid crystals. © 1985.

Endress, E., Heller, H., Casalta, H., Brown, M. F., & Bayerl, T. M. (2002). Anisotropic motion and molecular dynamics of cholesterol, lanosterol, and ergosterol in lecithin bilayers studied by quasi-elastic neutron scattering. Biochemistry, 41(43), 13078-13086.

PMID: 12390036;Abstract:

Quasi-elastic neutron scattering (QENS) was employed to study the molecular dynamics of three structurally related sterols, namely, cholesterol, lanosterol, and ergosterol. Oriented bilayers of dipalmitoylphosphatidylcholine (DPPC) were investigated at 40 mol % sterol content and at three temperatures (20, 36, and 50 °C) for two energy resolutions. Data analysis was concentrated on a direct comparison of the out-of-plane and the in-plane high-frequency motions of the three sterols in terms of their rates and amplitudes. The (spatially restricted) diffusive motion of the three sterols in the two directions was characterized by diffusion constants in the range of (5-30) x 10-12 m2 s-1, with a significantly faster rate of diffusion along the membrane normal, resulting in a diffusional anisotropy, Da. At low temperature (20 °C), cholesterol showed the highest value (Da = 4.5), while lanosterol gave the lowest one (Da = 2.0). At high temperature (50 °C), ergosterol diffusion had the highest diffusion anisotropy (Da = 2.0) compared to lanosterol (Da = 1.8) and cholesterol (Da = 1.6). Most interestingly, cholesterol showed at all three temperatures an amplitude of its out-of-plane-motion of 1.0-1.1 nm, more than a factor of 3 higher than measured for the other two sterols. This finding suggests that the short alkyl chain of the cholesterol molecule may cross at high frequency the bilayer midplane, while the other two sterols remain confined within the geometrical limits of each monolayer leaflet. The results provide an example of how slight structural alterations of sterols can affect their molecular dynamics in bilayers, which in turn may be relevant to the membrane micromechanical properties.

Mallikarjunaiah, K. J., Kinnun, J. J., Petrache, H. I., & Brown, M. F. (2013). Area per Lipid and Elastic Deformation of Membrane Bilayers Under Osmotic Stress. Biophysical Journal, 104, 588.
Job, C., Zajicek, J., & Brown, M. F. (1996). Fast field-cycling nuclear magnetic resonance spectrometer. Review of Scientific Instruments, 67(6), 2113-2122.

Abstract:

We describe here the design and construction of a modern, state-of-the-art nuclear magnetic resonance (NMR) field-cycling instrument. Fourier transform NMR spectra of both liquid and solid samples can be measured, and spin-lattice relaxation times (T1Z) investigated over a broad range of magnetic field strengths ranging from 0 to 2 T. The instrument is based upon an existing personal computer-based NMR spectrometer [C. Job, R. M. Pearson, and M. F. Brown, Rev. Sci. Instrum. 65, 3354 (1994)] which has been expanded into a fully computer-controlled field-cycling instrument. The magnetic field cycling is accomplished electronically by utilizing fast switching thyristors and a storage capacitor based on the Redfield energy storage concept. Unique aspects of the design include the field-cycling magnet, which can reach fields as high as 2 T; the personal computer-based NMR spectrometer and associated waveform electronics; and the use of a commercially available pulse width modulation switching current amplifier, having low internal power dissipation and a fast current settling time. Using this new technology T1Z relaxation times as short as 1 ms can be readily measured. © 1996 American Institute of Physics.

Brownholland, D. P., Longo, G. S., Struts, A. V., Justice, M. J., Szleifer, I., Petrache, H. I., Brown, M. F., & Thompson, D. H. (2009). Phase separation in binary mixtures of bipolar and monopolar lipid dispersions revealed by 2H NMR spectroscopy, small angle x-ray scattering, and molecular theory. Biophysical Journal, 97(10), 2700-2709.

PMID: 19917223;PMCID: PMC2776299;Abstract:

Binary mixtures of C20BAS and POPC membranes were studied by solid-state 2H NMR spectroscopy and small angle x-ray scattering (SAXS) over a wide range of concentrations and at different temperatures. Three specifically deuterated C20BAS derivatives-[1′,1′, 20′,20′-2H4]C20BAS, [2′,2′,19′,19′-2H4]C 20BAS, and [10′,11′-2H2]C 20BAS - combined with protiated 1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC), as well as membranes containing POPC-d31 and fully protiated bolalipid, were used in NMR experiments to obtain structural information for the mixtures. The 2H NMR spectra of [10′,11′-2H2]C20BAS/POPC membrane dispersions reveal that the bolalipid is predominantly in the transmembrane conformation at high bolalipid concentrations (100, 90, and 70 mol %). At ≤50 mol % C20BAS, smaller quadrupolar couplings appear in the spectra, indicating the presence of U-shaped conformers. The proportion of U-shaped bolalipids increases as the amount of POPC in the membrane increases; however, the transmembrane component remains the dominant bolalipid conformation in the membrane even at 45°C and 10 mol % C20BAS, where it accounts for ∼50% of the bolalipid population. The large fraction of C20BAS transmembrane conformers, regardless of the C20BAS/POPC ratio, together with the findings from molecular mean-field theory calculations, suggests the coexistence of phase-separated bolalipid-rich domains and POPC-rich domains. A single lamellar repeat distance was observed in SAXS experiments corresponding to the average repeat spacing expected for C20BAS-and POPC-rich domains. These observations are consistent with the presence of microphase-separated domains in the mixed membrane samples that arise from POPC-C20BAS hydrophobic mismatch. © 2009 by the Biophysical Society.