Biophysics
The Biophysics Research Group investigates host–pathogen interactions at the molecular level to elucidate the underlying structure–function mechanisms. We decipher and characterize bacterial and human membranes, with a particular focus on lung-relevant mycobacteria and Gram-negative bacteria, as well as their interactions with peptides and proteins. A major focus lies on investigating novel modes of action of membrane-active substances such as antimicrobial peptides and bacterial toxins. Our goal is not only to identify antimicrobial resistance (AMR), but also to develop new therapeutic concepts. In addition, we study the role of the membrane as the outer barrier of bacteria in bioactive aerosols. In this context, we analyze their properties and develop methods for the detection of pathogens in aerosols.
Starting from biomedical research questions, which we frequently address in collaboration with partners at FZB, LCI, CSSB, as well as within national and international networks, we employ various membrane models and combine them with state-of-the-art biophysical methods.
1) Membrane structure:
The basis of all investigations is the characterization of lipid membranes. Electrical and mechanical properties of membranes, as well as their lateral and transverse organization, play a key role. We study these properties in both natural membranes and reconstituted systems. To achieve this, we have expertise in the purification of lipids from natural membranes and in the targeted reconstitution of membranes. Chemical characterization is carried out in collaboration with the Bioanalytical Chemistry Research Group. Mycobacterial lipid membranes play a central role in our project “Intracellular membrane organization in Mycobacterium-infected cells”, which is part of the Leibniz Research Campus InterACt. Liposomes are specifically generated using microfluidics, and their interactions with active compounds are characterized.
2) Pore-forming antimicrobial substances:
We work on characterizing the function of antimicrobial peptides (AMPs), potential resistance mechanisms, and synergistic effects. We have succeeded in describing a novel mechanism of action for AMPs. Endotoxin-neutralizing activity is achieved not only through direct interaction of AMPs with endotoxins, but also through modification of receptor complexes embedded in the host cell membrane. Together with partners, we develop peptide-based novel AMPs with species-specific activity and without cytotoxic side effects.
3) Microbial toxins:
Membrane-active peptides can not only be used against pathogens; microorganisms also employ them against human cells. We investigate the mechanisms of action of the mycobacterial ESAT6/CFP10 complex and other WXG proteins. In addition, within several networks we collaborate on the characterization of, for example, candidalysin, PLAs, and VapA. In particular, elucidating species specificity plays a decisive role in understanding why AMPs and toxins, despite very similar mechanisms of action, target different membrane structures.
4) Microbial adhesion:
Bacteria and other microorganisms bind to surfaces via a wide range of mechanisms. These surfaces can be host cells or technical surfaces such as implants. Based on our expertise in performing binding measurements, we have been collaborating for many years with the research group of Iris Bruchhaus at BNITM to investigate the binding of malaria-infected erythrocytes to epithelial cells.
5) Infectious aerosols:
Building on a project funded by the Leibniz Research Network “Infections 21”, we have significantly expanded our expertise in the field of aerosols in recent years. Two projects are briefly highlighted here:
a) Dustrisk: In this project funded by the Leibniz Association, the infectivity of desert dust particles was investigated within a large consortium together with researchers from Leibniz institutes and clinicians in Cape Verde. Our contribution focused on characterizing microbial adhesion to dust particles.
b) Aerofix: Together with the research group “Molecular and Experimental Mycobacteriology” and the National Reference Center for Mycobacteria, we worked on a project funded by the Else Kröner Fresenius Foundation. In this project, we generate and characterize model aerosols and, together with the University of Münster, aim to establish a graphene-based sensor system for diagnostics.
6) Therapeutic aerosols:
To further advance the therapeutic application of AMPs, we have begun to characterize peptide interactions with lipid monolayers as a model of pulmonary surfactant monolayers. This requires the construction of a film balance equipped with a nebulization system, enabling the application of known drugs that are administered therapeutically via the lung. Together with the group of Regina Scherließ (University of Kiel), we have successfully developed a new device for characterizing the mechanical stability of drug pellets administered as aerosols.
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2025–2029 |
Leibniz Research Alliance Infections; Project title: “Polymicrobial lung infections, interactions with viral pathogens and therapeutic control of biofilms” |
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2025–2028 |
KIF funding at CSSB; Project title: “TARGET-MYCO – Peptide-Enhanced Targeting and Eradication of Mycobacterium tuberculosis” |
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2025–2027 |
NHMRC; Project title: “Preclinical validation of anti-tubercular conjugated oligoelectrolytes” |
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2024–2027 |
Leibniz Collaborative Excellence; Project title: “High-resolution analysis of synergistic effects between membrane-active peptides and classical antibiotics on bacterial membranes” |
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2024–2027 |
Leibniz Science Campus InterACt; Project title: “Organization of intracellular membrane in Mycobacteria-infected cells” |
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2022–2027 |
DFG-SPP2332; Project title: “Cytoadherence of Plasmodium-infected erythrocytes” |
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2024–2026 |
BMBF, DATIpilot Innovation Sprint funding line: “AspidaWund: Anti-infective and anti-inflammatory agent against wound infections” |
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2023–2026 |
Phospholipid Research Center, Heidelberg: “Liposome-based microfluidic platform for standardized analysis of antibacterial compounds” |
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2023–2024 |
Start-up Project in the DFG SPP 2225 Exit Strategies of Intracellular Pathogens: “Microfluidic encapsulation of pathogens to study their exit: A bottom-up model system for intracellular compartments” |
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2021–2023 |
DFG-SPP2225; Project title: “Inside out – The role of mycobacterial ESX secretion systems in phagosome escape” |
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2020–2023 |
Leibniz Collaborative Excellence; Project title: “A risk index for health effects of mineral dust and associated microbes” |
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2018–2019 |
Phospholipid Research Center; Project title: “Bottom-up designed synthetic bacteria – a tool to develop new antibiotic strategies” |
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2015–2020 |
Leibniz Research Alliance Infections’21 |
Membrane reconstitution techniques
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Small unilamellar liposomes (SUVs)
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Giant unilamellar liposomes (GUVs)
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Microfluidic liposome generation
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Pore-spanning membranes
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Solid-supported membranes
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Langmuir–Blodgett transfer
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Generation of asymmetric lipid membranes
Imaging techniques
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Atomic force microscopy (at FZB and CSSB, Hamburg)
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Electron microscopy (at CSSB, Hamburg)
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Fluorescence microscopy
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Microfluidics
Electrical techniques
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Reconstituted planar membranes
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Impedance spectroscopy on membranes
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Zeta potential
Protein–lipid interaction techniques
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Fluorescence spectroscopy
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Langmuir film balance
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Lipid State Observer (LISO)
X-ray techniques
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Reflectivity
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Small-angle X-ray scattering (SAXS)
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Grazing-incidence small-angle X-ray scattering (GISAXS)
Aerosol generation and characterization
Lipid and protein purification and characterization
Microbiology and cell biology
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Antibacterial and cytotoxicity tests
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Cell culture systems and cytokine induction (ELISA)
2025
Andrä, J, Aisenbrey, C, Sudheendra, US, Prudhon, M, Brezesinski, G, Zschech, C, Willumeit-Römer, R, Leippe, M, Gutsmann, T & Bechinger, B 2025, 'Corrigendum to "Structural analysis of the NK-lysin-derived peptide NK-2 upon interaction with bacterial membrane mimetics consisting of phosphatidylethanolamine and phosphatidylglycerol" [BBA - Biomembranes 1866 (2024) 184267]', BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, S. 184416. https://doi.org/10.1016/j.bbamem.2025.184416
Cronshagen, J, Allweier, J, Mesén-Ramírez, JP, Stäcker, J, Vaaben, AV, Ramón-Zamorano, G, Naranjo-Prado, I, Graser, M, López-Barona, P, Ofori, S, Jansen, PWTC, Hornebeck, J, Kieferle, F, Murk, A, Martin, E, Castro-Peña, C, Bártfai, R, Lavstsen, T, Bruchhaus, I & Spielmann, T 2025, 'A system for functional studies of the major virulence factor of malaria parasites', eLife, Jg. 13. https://doi.org/10.7554/eLife.103542
Rossetti, P, Trollmann, MFW, Wichmann, C, Gutsmann, T, Eggeling, C & Böckmann, RA 2025, 'From Membrane Composition to Antimicrobial Strategies: Experimental and Computational Approaches to AMP Design and Selectivity', Small (Weinheim an der Bergstrasse, Germany), S. e2411476. https://doi.org/10.1002/smll.202411476
2024
Allweier, J, Bartels, M, Torabi, H, Tauler, MDPM, Metwally, NG, Roeder, T, Gutsmann, T & Bruchhaus, I 2024, 'Cytoadhesion of Plasmodium falciparum-Infected Red Blood Cells Changes the Expression of Cytokine-, Histone- and Antiviral Protein-Encoding Genes in Brain Endothelial Cells', MOLECULAR MICROBIOLOGY. https://doi.org/10.1111/mmi.15331
Müller, R, König, A, Groth, S, Zarnowski, R, Visser, C, Handrianz, T, Maufrais, C, Krüger, T, Himmel, M & Lee, S et al. 2024, 'Secretion of the fungal toxin candidalysin is dependent on conserved precursor peptide sequences', Nature Microbiology, Jg. 9, Nr. 3, S. 669-683. https://doi.org/10.1038/s41564-024-01606-z
Nehls, C, Schröder, M, Haubenthal, T, Haas, A & Gutsmann, T 2024, 'The mechanistic basis of the membrane-permeabilizing activities of the virulence-associated protein A (VapA) from Rhodococcus equi', MOLECULAR MICROBIOLOGY, Jg. 121, Nr. 3, S. 578-592. https://doi.org/10.1111/mmi.15233
Gutsmann, T 2024, '"Meet the IUPAB councilor"-Thomas Gutsmann', Biophysical reviews, Jg. 16, Nr. 5, S. 515-517. https://doi.org/10.1007/s12551-024-01226-1
Sae-Ueng, U, Bunsuwansakul, C, Showpanish, K, Phironrit, N, Thadajarassiri, J & Nehls, C 2024, 'Nanomechanical resilience and thermal stability of RSJ2 phage', Scientific Reports, Jg. 14, Nr. 1, S. 19389. https://doi.org/10.1038/s41598-024-70056-8
Schaefer, S, Vij, R, Sprague, JL, Austermeier, S, Dinh, H, Judzewitsch, PR, Müller-Loennies, S, Lopes Silva, T, Seemann, E & Qualmann, B et al. 2024, 'A synthetic peptide mimic kills Candida albicans and synergistically prevents infection', Nature communications, Jg. 15, Nr. 1, S. 6818. https://doi.org/10.1038/s41467-024-50491-x
Schromm, AB, Correa, W, Gisch, N, Steiniger, F, Richter, W, Martinez-de-Tejada, G, Brandenburg, K & von Wintzingerode, F 2024, 'Supramolecular assembly of micellar aggregates is the basis of low endotoxin recovery (LER) in a drug formulation that can be resolved by a whole blood assay', Biomedicine & pharmacotherapy, Jg. 173, S. 116286. https://doi.org/10.1016/j.biopha.2024.116286
2023
Andrä, J, Aisenbrey, C, Sudheendra, US, Prudhon, M, Brezesinski, G, Zschech, C, Willumeit-Römer, R, Leippe, M, Gutsmann, T & Bechinger, B 2024, 'Structural analysis of the NK-lysin-derived peptide NK-2 upon interaction with bacterial membrane mimetics consisting of phosphatidylethanolamine and phosphatidylglycerol', BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, Jg. 1866, Nr. 3, S. 184267. https://doi.org/10.1016/j.bbamem.2023.184267
Donoghue, A, Winterhalter, M & Gutsmann, T 2023, 'Influence of Membrane Asymmetry on OmpF Insertion, Orientation and Function', Membranes, Jg. 13, Nr. 5, 517. https://doi.org/10.3390/membranes13050517
2022
Al Nahas, K, Fletcher, M, Hammond, K, Nehls, C, Cama, J, Ryadnov, MG & Keyser, UF 2022, 'Measuring Thousands of Single-Vesicle Leakage Events Reveals the Mode of Action of Antimicrobial Peptides', ANALYTICAL CHEMISTRY , Jg. 94, Nr. 27, S. 9530-9539. https://doi.org/10.1021/acs.analchem.1c03564
Bachmann, A, Metwally, NG, Allweier, J, Cronshagen, J, Del Pilar Martinez Tauler, M, Murk, A, Roth, LK, Torabi, H, Wu, Y, Gutsmann, T & Bruchhaus, I 2022, 'CD36-A Host Receptor Necessary for Malaria Parasites to Establish and Maintain Infection', Microorganisms, Jg. 10, Nr. 12, S. 2356. https://doi.org/10.3390/microorganisms10122356
Blackler, RJ, Müller-Loennies, S, Pokorny-Lehrer, B, Legg, MSG, Brade, L, Brade, H, Kosma, P & Evans, SV 2022, 'Antigen binding by conformational selection in near-germline antibodies', The Journal of biological chemistry, Jg. 298, Nr. 5, S. 101901. https://doi.org/10.1016/j.jbc.2022.101901
Hansen, J, Kolbe, K, König, IR, Scherließ, R, Hellfritzsch, M, Malm, S, Müller-Loennies, S, Zallet, J, Hillemann, D, Wiesmüller, K-H, Herzmann, C, Brandenburg, J & Reiling, N 2022, 'Lipobiotin-capture magnetic bead assay for isolation, enrichment and detection of Mycobacterium tuberculosis from saliva', PLOS ONE, Jg. 17, Nr. 7, S. e0265554. https://doi.org/10.1371/journal.pone.0265554
Lagune, M, Le Moigne, V, Johansen, MD, Vásquez Sotomayor, F, Daher, W, Petit, C, Cosentino, G, Paulowski, L, Gutsmann, T, Wilmanns, M, Maurer, FP, Herrmann, J-L, Girard-Misguich, F & Kremer, L 2022, 'The ESX-4 substrates, EsxU and EsxT, modulate Mycobacterium abscessus fitness', PLOS PATHOGENS, Jg. 18, Nr. 8, S. e1010771. https://doi.org/10.1371/journal.ppat.1010771
Mogavero, S, Höfs, S, Lauer, AN, Müller, R, Brunke, S, Allert, S, Gerwien, F, Groth, S, Dolk, E, Wilson, D, Gutsmann, T & Hube, B 2022, 'Candidalysin Is the Hemolytic Factor of Candida albicans', Toxins, Jg. 14, Nr. 12, 874. https://doi.org/10.3390/toxins14120874
Möller, C, Heinbockel, L, Garidel, P, Gutsmann, T, Mauss, K, Weindl, G, Fukuoka, S, Loser, D, Danker, T & Brandenburg, K 2022, 'Toxicological and Safety Pharmacological Profiling of the Anti-Infective and Anti-Inflammatory Peptide Pep19-2.5', Microorganisms, Jg. 10, Nr. 12, S. 2412. https://doi.org/10.3390/microorganisms10122412
Palusińska-Szysz, M, Jurak, M, Gisch, N, Waldow, F, Zehethofer, N, Nehls, C, Schwudke, D, Koper, P & Mazur, A 2022, 'The human LL-37 peptide exerts antimicrobial activity against Legionella micdadei interacting with membrane phospholipids', BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, Jg. 1867, Nr. 6, S. 159138. https://doi.org/10.1016/j.bbalip.2022.159138
Roeckendorf, N, Nehls, C & Gutsmann, T 2022, 'Design of Membrane Active Peptides Considering Multi-Objective Optimization for Biomedical Application', Membranes, Jg. 12, Nr. 2, 12020180. https://doi.org/10.3390/membranes12020180
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