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Paulo Almeida

The Lab

Membrane domains
Lipid domains can form in bilayer membranes with two or more components. Addition of peripheral proteins further modulates lipid domain formation. We seek to determine the interactions responsible for lipid domain formation, in particular in membranes containing cholesterol, using a combination of Monte Carlo simulations, fluorescence spectroscopy and imaging, and differential scanning calorimetry. This project has been funded by Research Corporation.

Mechanism of antimicrobial, cytolytic, and cell-penetrating peptides
Amphipathic, alpha-helical peptides represent an important class of antimicrobial, cytolytic, and cell-penetrating peptides. Their specificities are different but they function by direct interaction with the lipid bilayer of their target cell membranes. Our goal is to understand the mechanism of these peptides and how their activity is related to their sequence. This project has been carried out in collaboration with Antje Pokorny and Hee-Seung Lee, and has been funded by the NIH.

Selected Publications
Almeida, P. F. F., Vaz, W. L. C., and Thompson, T. E.(1992). Lateral diffusion in the liquid phases of dimyristoylphosphatidylcholine/cholesterol lipid bilayers: a free volume analysis. Biochemistry 31, 6739–6747.

Pokorny, A., H. Birkbeck, and P.F.F. Almeida (2002). Mechanism and Kinetics of d-lysin interaction with phospholipid vesicles. Biochemistry 41, 11044-11056.

Pokorny, A., and Almeida P.F. (2004). Kinetics of dye efflux and lipid flip-flop induced  by 
d-lysin in phosphatidylcholine vesicles and the mechanism of graded release by amphipathic, alpha-helical peptides. Biochemistry 43, 8846-8857.

Frazier, M.L., Wright, J.R., Pokorny, A., and Almeida, P.F.F. (2007). Investigation of domain formation in sphingomyelin/cholesterol/POPC mixtures by fluorescence resonance energy transfer and Monte Carlo simulations. Biophys. J. 92, 2422-2433.

Yandek, L.E., Pokorny, A., Floren, A., Knoelke, K., Langel, U., and Almeida, P.F.F (2007). Mechanism of the cell-penetrating peptide transportan 10 permeation of lipid bilayers. Biophys J. 92, 2434-2444.

Gregory, S.M., Cavenaugh, A., Journigan, V., Pokorny, A., and Almeida, P.F. (2008). A quantitative model for the all-or-none permeabilization of phospholipid vesicles by the antimicrobial peptide cecropin A. Biophys. J. 94, 1667-1680.

Almeida P.F.F. (2009) Thermodynamics of lipid interactions in complex bilayers. Biochim Biophys Acta 1788, 72-85.

Gregory, S.M., A. Pokorny, and P.F.F. Almeida (2009) Magainin 2 revisited: a test of the quantitative model for the all-or-none permeabilization of phospholipid vesicles. Biophys. J. 96, 116-131.

Almeida, P.F, and A. Pokorny (2009) Mechanism of antimicrobial, cytolytic, and cell-penetrating peptides: From kinetics to thermodynamics. Biochemistry 48, 8083-8093.

Almeida, P.F. (2011) A simple thermodynamic model of the liquid-ordered state and the interactions between phospholipids and cholesterol. Biophys. J. 100:420-429

McKeown, A.N., Naro, J.L., Huskins, L.J., and Almeida, P.F. (2011) A thermodynamic approach to the mechanism of cell-penetrating peptides in model membranes. Biochemistry 50:654-662.

Clark, K.S., Svetlovics, J., McKeown, A.N., Huskins L, Almeida PF. (2011). What determines the activity of antimicrobial and cytolytic peptides in model membranes. Biochemistry 50:7919-7932.

Almeida, P.F., Best, A., and Hinderliter, A. (2011) Monte Carlo simulation of protein-induced lipid demixing in a membrane with interactions derived from experiment. Biophys J. 101:1930-1937.

Almeida, P.F., Ladokhin, A.S., and White, S.H. (2012) Hydrogen-bond energetics drive helix formation in membrane interfaces. Biochim Biophys Acta. 1818:178-182.

Frazier et al. (2007).

Almeida & Pokorny (2009).

Pokorny et al. (2002).

Where students went

Monica Frazier, PhD student, University of North Carolina at Chapel Hill.

Lindsay Yandek, PhD student, Case Western University.

Sonia Gregory, PhD student, University of Virginia.

Alesia McKeown, PhD student, University of Oregon.