TY - JOUR AU - Kiss, Bálint AU - Kellermayer, Miklós TI - Packing up the genome JF - ELIFE J2 - ELIFE VL - 12 PY - 2023 PG - 3 SN - 2050-084X DO - 10.7554/eLife.94128 UR - https://m2.mtmt.hu/api/publication/34452952 ID - 34452952 AB - Nucleotide and force-dependent mechanisms control how the viral genome of lambda bacteriophage is inserted into capsids. LA - English DB - MTMT ER - TY - THES AU - Kiss, Bálint TI - STRUCTURE, NANOMECHANICS AND INFECTION DYNAMICS OF SINGLE VIRUS PARTICLES PY - 2023 DO - 10.14753/SE.2023.2799 UR - https://m2.mtmt.hu/api/publication/34444219 ID - 34444219 LA - English DB - MTMT ER - TY - JOUR AU - Nonn, A. AU - Kiss, Bálint AU - Pezeshkian, W. AU - Tancogne-Dejean, T. AU - Cerrone, A. AU - Kellermayer, Miklós AU - Bai, Y. AU - Li, W. AU - Wierzbicki, T. TI - Inferring mechanical properties of the SARS-CoV-2 virus particle with nano-indentation tests and numerical simulations JF - JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS J2 - J MECH BEHAV BIOMED VL - 148 PY - 2023 PG - 15 SN - 1751-6161 DO - 10.1016/j.jmbbm.2023.106153 UR - https://m2.mtmt.hu/api/publication/34231576 ID - 34231576 LA - English DB - MTMT ER - TY - JOUR AU - Szebeni, János AU - Kiss, Bálint AU - Bozó, Tamás AU - Turjeman, Keren AU - Levi-Kalisman, Yael AU - Barenholz, Yechezkel AU - Kellermayer, Miklós TI - Insights into the Structure of Comirnaty Covid-19 Vaccine: A Theory on Soft, Partially Bilayer-Covered Nanoparticles with Hydrogen Bond-Stabilized mRNA–Lipid Complexes JF - ACS NANO J2 - ACS NANO VL - 17 PY - 2023 IS - 14 SP - 13147 EP - 13157 PG - 11 SN - 1936-0851 DO - 10.1021/acsnano.2c11904 UR - https://m2.mtmt.hu/api/publication/34058342 ID - 34058342 N1 - Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, Budapest, 1089, Hungary Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health Sciences, Miskolc University, Miskolc, 2880, Hungary School of Chemical Engineering and Translational Nanobioscience Research Center, Sungkyunkwan University, Suwon, 16419, South Korea Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, 1094, Hungary Hungarian Centre of Excellence for Molecular Medicine (HCEMM), In Vivo Imaging Advanced Core Facility, Budapest, 1094, Hungary ELKH-SE Biophysical Virology Research Group, Budapest, 1094, Hungary The Laboratory of Membrane and Liposome Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, 9112102, Israel Institute of Life Sciences and the Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 9190401, Israel Export Date: 19 October 2023 Correspondence Address: Szebeni, J.; Nanomedicine Research and Education Center, Hungary; email: jszebeni2@gmail.com LA - English DB - MTMT ER - TY - GEN AU - Szebeni, János AU - Kiss, Bálint AU - Tamás, Bozó AU - Keren, Turjeman AU - Yael, Levi-Kalisman AU - Yechezkel, Barenholz AU - Kellermayer, Miklós TI - New insights into the structure of Comirnaty Covid-19 vaccine: A theory on soft nanoparticles with mRNA-lipid supercoils stabilized by hydrogen bonds PY - 2022 UR - https://m2.mtmt.hu/api/publication/34044110 ID - 34044110 AB - Despite the worldwide success of mRNA-LNP Covid-19 vaccines, the nanoscale structure of these formulations is still poorly understood. To fill this gap, we used a combination of atomic force microscopy (AFM), dynamic light scattering (DLS), transmission electron microscopy (TEM), cryogenic transmission electron microscopy (cryo-TEM) and the determination of LNP pH gradient to analyze the nanoparticles (NPs) in BNT162b2 (Comirnaty), comparing it with the well characterized pegylated liposomal doxorubicin (Doxil). Comirnaty NPs had similar size to Doxil, however, unlike Doxil liposomes, wherein the stable ammonium and pH gradient enables accumulation of 14C-methylamine in the intraliposomal aqueous phase, Comirnaty LNPs lack such pH gradient in spite of the fact that the pH 4, at which LNPs are prepared, is raised to pH 7.2 after loading of the mRNA. Mechanical manipulation of Comirnaty NPs with AFM revealed soft, compliant structures. The sawtooth-like force transitions seen during cantilever retraction implies that molecular strands, corresponding to mRNA, can be pulled out of NPs, and the process is accompanied by stepwise rupture of mRNA-lipid bonds. Unlike Doxil, cryo-TEM of Comirnaty NPs revealed a granular, solid core enclosed by mono- and bilayers. Negative staining TEM shows 2-5 nm electron-dense spots in the liposom’s interior that are aligned into strings, semicircles, or labyrinth-like networks, which may imply crosslink-stabilized supercoils. The neutral intra-LNP core questions the dominance of ionic interactions holding together this scaffold, raising the alternative possibility of hydrogen bonding between the mRNA and the lipids. Such interaction, described previously for another mRNA/lipid complex, is consistent with the steric structure of ionizable lipid in Comirnaty, ALC-0315, displaying free =O and -OH groups. It is hypothesized that the latter groups can get into steric positions that enable hydrogen bonding with the nitrogenous bases in the mRNA. These newly recognized structural features of mRNA-LNP may be important for the vaccine’s efficacy.Competing Interest StatementThe authors have declared no competing interest. LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Bálint AU - Kiss, Luca Annamária AU - Lohinai, Zsombor Dávid AU - Mudra, Dorottya Mária AU - Tordai, Hedvig AU - Herényi, Levente AU - Csik, Gabriella AU - Kellermayer, Miklós TI - Imaging the Infection Cycle of T7 at the Single Virion Level JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 19 PG - 13 SN - 1661-6596 DO - 10.3390/ijms231911252 UR - https://m2.mtmt.hu/api/publication/33119125 ID - 33119125 AB - T7 phages are E. coli-infecting viruses that find and invade their target with high specificity and efficiency. The exact molecular mechanisms of the T7 infection cycle are yet unclear. As the infection involves mechanical events, single-particle methods are to be employed to alleviate the problems of ensemble averaging. Here we used TIRF microscopy to uncover the spatial dynamics of the target recognition and binding by individual T7 phage particles. In the initial phase, T7 virions bound reversibly to the bacterial membrane via two-dimensional diffusive exploration. Stable bacteriophage anchoring was achieved by tail-fiber complex to receptor binding which could be observed in detail by atomic force microscopy (AFM) under aqueous buffer conditions. The six anchored fibers of a given T7 phage-displayed isotropic spatial orientation. The viral infection led to the onset of an irreversible structural program in the host which occurred in three distinct steps. First, bacterial cell surface roughness, as monitored by AFM, increased progressively. Second, membrane blebs formed on the minute time scale (average ~5 min) as observed by phase-contrast microscopy. Finally, the host cell was lysed in a violent and explosive process that was followed by the quick release and dispersion of the phage progeny. DNA ejection from T7 could be evoked in vitro by photothermal excitation, which revealed that genome release is mechanically controlled to prevent premature delivery of host-lysis genes. The single-particle approach employed here thus provided an unprecedented insight into the details of the complete viral cycle. LA - English DB - MTMT ER - TY - CONF AU - Kretzer, Balázs Dávid AU - Herényi, Levente AU - Csik, Gabriella AU - Kiss, Bálint AU - Kellermayer, Miklós TI - Porphyrin binding by DNA as a function of ionic strength and chain mechanics T2 - PhD Scientific Days 2022 PY - 2022 SP - 1 UR - https://m2.mtmt.hu/api/publication/33029705 ID - 33029705 LA - English DB - MTMT ER - TY - JOUR AU - Mudra, Dorottya Mária AU - Kiss, Bálint AU - Kis, Zoltán AU - Pályi, Bernadett AU - Kellermayer, Miklós TI - Structure, dynamics and nanomechanics of wild-type and alpha-variant SARS-CoV-2 virions JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 121 PY - 2022 IS - 3 SP - 419a EP - 419a SN - 0006-3495 DO - 10.1016/j.bpj.2021.11.683 UR - https://m2.mtmt.hu/api/publication/32853652 ID - 32853652 LA - English DB - MTMT ER - TY - JOUR AU - Padányi, Rita AU - Farkas, Bianka Vivien AU - Tordai, Hedvig AU - Kiss, Bálint AU - Grubmüller, Helmut AU - Soya, Naoto AU - Lukács, Gergely L. AU - Kellermayer, Miklós AU - Hegedűs, Tamás TI - Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1 JF - COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL J2 - CSBJ VL - 20 PY - 2022 SP - 2587 EP - 2599 PG - 13 SN - 2001-0370 DO - 10.1016/j.csbj.2022.05.036 UR - https://m2.mtmt.hu/api/publication/32853643 ID - 32853643 AB - Cystic fibrosis (CF) is a frequent genetic disease in Caucasians that is caused by the deletion of F508 (DF508) in the nucleotide binding domain 1 (NBD1) of the CF transmembrane conductance regulator (CFTR). The DF508 compromises the folding energetics of the NBD1, as well as the folding of three other CFTR domains. Combination of FDA approved corrector molecules can efficiently but incompletely rescue the DF508-CFTR folding and stability defect. Thus, new pharmacophores that would reinstate the wildtype-like conformational stability of the DF508-NBD1 would be highly beneficial. The most prominent molecule, 5-bromoindole-3-acetic acid (BIA) that can thermally stabilize the NBD1 has low potency and efficacy. To gain insights into the NBD1 (un)folding dynamics and BIA binding site localization, we combined molecular dynamics (MD) simulations, atomic force spectroscopy (AFM) and hydrogendeuterium exchange (HDX) experiments. We found that the NBD1 a-subdomain with three adjacent strands from the b-subdomain plays an important role in early folding steps, when crucial non-native interactions are formed via residue F508. Our AFM and HDX experiments showed that BIA associates with this a-core region and increases the resistance of the DF508-NBD1 against mechanical unfolding, a phenomenon that could be exploited in future developments of folding correctors. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Bálint AU - Kis, Zoltán AU - Palyi, B AU - Kellermayer, Miklós TI - Az új típusú koronavírus nanobiofizikája JF - LEGE ARTIS MEDICINAE J2 - LEGE ART MED VL - 32 PY - 2022 IS - 3 SP - 147 EP - 152 PG - 6 SN - 0866-4811 DO - 10.33616/lam.32.013 UR - https://m2.mtmt.hu/api/publication/32819052 ID - 32819052 AB - A Covid-19-pandémia végigsöpört az egész világon, soha nem látott megterhelést okozva egészségügyi rendszereinkben, és kihívások elé állította a biomedicinális kutatást, hogy a járványra mielőbb megfelelő válaszokat adjunk. A modern „egy partikulum” biofizikai módszerek különleges bepillantást engednek a járvány okozója, a SARSCoV- 2 tulajdonságaiba. A vírus tüske fehérjékből álló koronaszerű réteget hordoz a felületén, melyeknek fontos szerepet tulajdonítunk a fertőzés folyamatában. Atomi erőmikroszkóp segítségével sikerült feltárnunk a natív virionok topográfiai szerkezetét és mechanikai tulajdonságait. A tüskefehérjék, rugalmasságuk és mozgékonyságuk révén, dinamikus felületet alkotnak. A virionok meglepően ellenállóak a mechanikai összenyomással szemben, és szerkezetük képes helyreállni a mechanikai behatást követően. A vírus globális szerkezete ellenáll a hőhatásnak, de a hőmérséklet fokozásával a tüskefehérjék disszociálódnak a felületről. A SARS-CoV-2 mechanikai és dinamikai sajátosságai hozzájárulnak fertőző képességéhez. Az alkalmazott „egy partikulum” biofizikai módszerek fontos szerepet játszhatnak az egyre gyakoribbá váló vírusfertőzések megértésében és legyőzésében. LA - Hungarian DB - MTMT ER -