Research in the Heberle lab is aimed at elucidating the structure and function of biological membranes, with a focus on the plasma membrane (PM). Just two lipid molecules thick, this oily sheet was long thought to be a simple barrier that protects a cell from its surroundings, providing structural integrity and enabling a regulated internal environment necessary for life's chemical reactions. However, new research is upending this simplistic viewpoint and replacing it with a more complicated one, in which the three-dimensional organization of hundreds of chemically distinct lipids and thousands of unique proteins plays an active role in the life of a cell.
Although the basic architecture of the PM has been known for nearly fifty years, there is an emerging consensus that some critical processes occurring at and within the plasma membrane cannot be adequately explained without invoking ultrastructure—that is, the fine details of lipid and protein spatial organization on the nanometer length scale. Our lab specializes in experiments capable of seeing membrane structure at this level of detail. Together with a strong international network of collaborators, we combine expertise in biophysical, biochemical, and computational methods to answer fundamental questions about biomembrane structure and organization. We use model systems spanning a vast range of complexity, from simple liposomes made from a single type of lipid, to multicomponent vesicles with engineered lipid asymmetry, to the plasma membrane of a living cell itself.
Fred Heberle received a B.A. in chemistry from Cornell University in 2003. In 2005, he joined the laboratory of Prof. Gerald Feigenson at Cornell where he studied phase separation in model membranes, earning a Ph.D. in biophysics in 2011. That was followed by postdoctoral research with Dr. John Katsaras in the Neutron Sciences Division at Oak Ridge National Lab (ORNL), where Dr. Heberle developed innovative neutron contrast variation methods to investigate the spatial organization of lipids in complex biomimetic membranes. In 2015, Dr. Heberle began a three-year appointment as a Research Scientist at the University of Tennessee/ORNL Joint Institute for Biological Sciences. During this time his research focused on developing robust methods for preparing artificial asymmetric membranes. In 2018, Dr. Heberle accepted a position as an Adjunct Professor in the Department of Integrative Biology and Pharmacology at the University of Texas Health Science Center in Houston where, in collaboration with Profs. Ilya Levental and Neal Waxham, he used cryogenic electron microscopy to visualize the nanoscopic structure of biomembranes. In 2019, Dr. Heberle joined the faculty at the University of Tennessee, where he is currently an Assistant Professor of physical chemistry.
B.A., Cornell University (2003)
Ph.D., Cornell University (2011)
Kelley EG,† Heberle FA.† 2022. Sensing a little friction. Biophysical Journal 121:2827-2829.
DiPasquale M, Deering TG, Desai D, Sharma AK, Amin S, Fox TE, Kester M, Katsaras J, Marquardt D, Heberle FA.† 2022. Influence of ceramide on lipid domain stability studied with small-angle neutron scattering: The role of acyl chain length and unsaturation. Chemistry and Physics of Lipids 245:105205.
Lewis-Laurent A, Doktorova M, Heberle FA,† Marquardt D.† 2021. Vesicle Viewer: Online visualization and analysis of small-angle scattering from lipid vesicles. Biophysical Journal 120:4639-4648.
Enoki TA, Wu J, Heberle FA, Feigenson GW. 2021. Investigation of the domain line tension in asymmetric vesicles prepared via hemifusion. Biochimica et Biophysica Acta 1863:183586.
Levental I, Levental K, Heberle FA. 2020. Lipid rafts: controversies solved, mysteries remain. Trends in Cell Biology 30:341-353.
Scott HL, Baker JR, Frederick AF, Kennison KB, Mendes K, Heberle FA.† 2020. FRET from phase-separated vesicles: An analytical solution for a spherical geometry. Chemistry and Physics of Lipids 233:104982.
Heberle FA,† Doktorova M, Scott HL, Skinkle A, Waxham MN,† Levental I.† 2020. Direct label-free imaging of nanodomains in biomimetic and biological membranes by cryogenic electron microscopy. Proceedings of the National Academy of Sciences of the USA 117:19943-19952.
Doktorova M, Kučerka N, Kinnun JJ, Pan J, Marquardt D, Scott HL, Venable RM, Pastor RW, Wassall SR, Katsaras J,† Heberle FA.† 2020. Molecular Structure of Sphingomyelin in Fluid Phase Bilayers Determined by the Joint Analysis of Small-Angle X-ray and Neutron Scattering Data. Journal of Physical Chemistry B 124:5186-5200.
Heberle FA. 2019. With lipid rafts, context is everything. Biophysical Journal 117:1549-1551.
Scott HL, Skinkle A, Kelley EG, Waxham MN, Levental I, Heberle FA.† 2019. On the mechanism of bilayer separation by extrusion; or, why your LUVs are not really unilamellar. Biophysical Journal 117:1381-1386.
Doktorova M,* Heberle FA,* Eicher B, Standaert RF, Katsaras J, London E, Pabst G, Marquardt D. 2018. Preparation of asymmetric phospholipid vesicles: The next generation of cell membrane models. Nature Protocols 13:2086-2101.
Heberle FA, Pabst G. 2017. Complex Biomembrane Mimetics on the Sub-Nanometer Scale. Biophysical Reviews 9:353-373.
Heberle FA,†* Marquardt D,†* Doktorova M,* Geier B,* Standaert RF, Heftberger P, Kollmitzer B, Nickels JD, Feigenson GW, Katsaras J, London E, Pabst G.† 2016. Subnanometer Structure of an Asymmetric Model Membrane: Interleaflet Coupling Influences Domain Properties. Langmuir 32:5195-5200.
Heberle FA,† Anghel VNP,† Katsaras J. 2015. Scattering from phase-separated vesicles I. An analytical form factor for multiple static domains. Journal of Applied Crystallography 48:1391-1404.
Heberle FA,†* Doktorova M,* Goh SL,* Standaert RF, Katsaras J, Feigenson GW.† 2013. Hybrid and Nonhybrid Lipids Exert Common Effects on Membrane Raft Size and Morphology. Journal of the American Chemical Society 135:14932-14935.
Heberle FA,† Petruzielo RS, Pan J, Drazba P, Kučerka N, Standaert RF, Feigenson GW, Katsaras J.† 2013. Bilayer Thickness Mismatch Controls Domain Size in Model Membranes. Journal of the American Chemical Society 135:6853-6859.
*Authors contributed equally †Corresponding author