It Takes More than Two to Tango: Complex, Hierarchal, and Membrane-Modulated Interactions in the Regulation of Receptor Tyrosine Kinases

Kovács T, Zákány F, Nagy P

Cancers, 14: 944. (2022)

Biophysical experiments reveal a protective role of protein phosphatase Z1 against oxidative damage of the cell membrane in Candida albicans

Hajdu T, Szabó K, Jakab Á, Pócsi I, Dombrádi V, Nagy P

Free Rad Biol Med, 176: 222-227. (2021)

In a collaborative study, the fungus-specific protein phosphatase Z1 (Ppz1) enzyme has been investigated and it was found to be crucial in the defence against oxidative stress. Researchers in the Department of Biophysics and Cell Biology, Department of Medical Chemistry and Department of Molecular Biotechnology and Microbiology proved that the deletion of the gene of Ppz1 leads to low membrane compactness and an increase in the sensitivity to oxidative challenge in Candida albicans cells. Examining the membrane fluidity-related generalized polarization reveals that while most native cells (WT) expressing Ppz1 were able to neutralize the effect of the applied oxidative agent, tert-butyl-hydroperoxide (tBOOH), mutant cells lacking Ppz1 expression (KO) suffered from latent oxidative damage and were characterized by incompact membrane. The lack of Ppz1 also manifests in increased membrane lipid peroxidation. Investigation of the lateral mobility of lipids revealed that the lack of Ppz1 combined with oxidative stress reduces the lateral diffusion of lipids resulting in reduced competitive fitness. According to these data, applying mild oxidative treatments together with prospective Ppz1 inhibitor molecules may tackle fungal infections caused by drug-resistant Candida albicans species. The study also revealed that changes in membrane characteristics may be used by fungal cells as a cue for responding to changes in the environment.


Statin-boosted cellular uptake and endosomal escape of penetratin due to reduced membrane dipole potential

Batta G, Kárpáti L, Henrique GF, Tóth G, Tarapcsák S, Kovács T, Zákány F, Mándity IM, Nagy P

Br J Pharmacol, 178: 3667-3681. (2021)

Research carried out in collaboration between the Department of Biophysics and Cell Biology, and the Department of Genetics of Applied Microbiology at the University of Debrecen, and the Department of Organic Chemistry, Semmelweis University revealed that cellular uptake of cell penetrating peptides (CPP) depends on the membrane dipole potential and that it can be enhanced by reducing the dipole potential. Cell penetrating peptides are molecules capable of traversing the intact cell membrane even when loaded with cargo, e.g. membrane impermeable drugs. The research group of Peter Nagy found that this uptake takes place by endocytosis followed by endosomal escape. Since most cell penetrating peptides are positively charged, the intramembrane, positive dipole potential generated by the ordered arrangement of dipoles in the membrane, inhibits their membrane crossing. Atorvastatin, widely applied in the treatment of high blood cholesterol levels, decreases the membrane dipole potential and consequently enhances the cellular uptake of cell penetrating peptides. The findings lay the foundation for applying the revealed principle for boosting the cellular uptake of drugs in the treatment of human diseases.


An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin

Zákány F, Szabó M, Batta G, Kárpáti L, Mándity M. István, Fülöp P, Varga Z, Panyi G, Nagy P, Kovács T

Frontiers in Cell and Developmental Biology 9: 647300. (2021)

I am the alpha and the ... gamma, and the G. Calibration of intensity-based FRET meaurements

Szabó Á, Nagy P

Cytometry, 99A: 369-371. (2021)

Comprehensive Model for Epidermal Growth Factor Receptor Ligand Binding Involving Conformational States of the Extracellular and the Kinase Domains

Hajdu T, Váradi T, Rebenku I, Kovács T, Szöllősi J, Nagy P.

Frontiers in Cell and Developmental Biology 8: 776. (2020)

Quo vadis FRET? Förster's method in the era of superresolution

Szabó Á, Szendi-Szatmári T, Szöllősi J, Nagy P

Methods and Applications in Fluorescence, 8(3): 032003. (2020)

Reducing the detrimental effects of saturation phenomena in FRET microscopy

Szendi-Szatmári T, Szabó Á, Szöllősi J, Nagy P

Anal Chem, 91: 6378-6382 (2019)

Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease

Batta G, Soltész L, Kovács T, Bozó T, Mészár Z, Kellermayer M, Szöllősi J, Nagy P.

Sci Rep. 8: 157 (2018)

The effect of fluorophore conjugation on antibody affinity and the photophysical properties of dyes

Szabó Á, Szenti-Szatmári T, Ujlaky-Nagy L, Rádi I, Vereb G, Szöllősi J, Nagy P.

Biophys J, 114:688-700 (2018)

The dipole potential correlates with lipid raft markers in the plasma membrane of living cells

Kovács T, Batta G, Zákány F, Szöllősi J, Nagy P.

J Lipid Res. 58(8):1681-1691 (2017)

The Dipole Potential Modifies the Clustering and Ligand Binding Affinity of ErbB Proteins and Their Signaling Efficiency

Kovács T, Batta G, Hajdu T, Szabó Á, Váradi T, Zákány F, Csomós I, Szöllősi J, Nagy P.

Sci Rep. 6:35850 (2016)

rFRET: A comprehensive, Matlab-based program for analyzing intensity-based ratiometric microscopic FRET experiments

Nagy P, Szabó Á, Váradi T, Kovács T, Batta G, Szöllősi J.

Cytometry A. 89(4):376-84 (2016)

Maximum likelihood estimation of FRET efficiency and its implications for distortions in pixelwise calculation of FRET in microscopy

Nagy P, Szabó A, Váradi T, Kovács T, Batta G, Szöllősi J.

Cytometry A. 85(11):942-52 (2014)

Epigallocatechin 3-O-gallate induces 67 kDa laminin receptor-mediated cell death accompanied by downregulation of ErbB proteins and altered lipid raft clustering in mammary and epidermoid carcinoma cells

Mocanu MM, Ganea C, Georgescu L, Váradi T, Shrestha D, Baran I, Katona E, Nagy P, Szöllősi J.

J Nat Prod. 77(2):250-7 (2014)

Binding of trastuzumab to ErbB2 is inhibited by a high pericellular density of hyaluronan

Váradi T, Mersich T, Auvinen P, Tammi R, Tammi M, Salamon F, Besznyák I Jr, Jakab F, Baranyai Z, Szöllősi J, Nagy P.

J Histochem Cytochem. 60(8):567-75 (2012)

Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine kinases in living cells using number and brightness analysis

Nagy P, Claus J, Jovin TM, Arndt-Jovin DJ.

Proc Natl Acad Sci U S A. 107(38):16524-9 (2010)

Coclustering of ErbB1 and ErbB2 revealed by FRET-sensitized acceptor bleaching

Szabó A, Szöllősi J, Nagy P.

Biophys J. 99(1):105-14 (2010)

Quantitative characterization of the large-scale association of ErbB1 and ErbB2 by flow cytometric homo-FRET measurements

Szabó A, Horváth G, Szöllősi J, Nagy P.

Biophys J. 95(4):2086-96 (2008)

EGFR and ErbB2 are functionally coupled to CD44 and regulate shedding, internalization and motogenic effect of CD44

Pályi-Krekk Z, Barok M, Kovács T, Saya H, Nagano O, Szöllősi J, Nagy P.

Cancer Lett. 263(2):231-42 (2008)

Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer

Pályi-Krekk Z, Barok M, Isola J, Tammi M, Szöllősi J, Nagy P.

Eur J Cancer. 43(16):2423-33 (2007)