Molecular Spectroscopy for BioMedical Studies

Research project objectives/Hypothesis

Interdisciplinary research, at the interface of medicinal biology and molecular biophysics will be carried out, aimed to unveil molecular mechanisms responsible for the severe toxic side effects of antifungal antibiotic amphotericin B (AmB). This antibiotic belongs to the group of life saving pharmaceuticals and despite of its nephrotoxicity and hepatotoxicity is used for treatment of deep seated mycotic infections due to its effectiveness. The main objective of the project is unveiling and understanding of molecular mechanisms responsible for AmB toxicity, in particular, verification of our working hypothesis based on the results of our pilot studies. According to this hypothesis:

Amphotericin B molecules, in water environment, self-organize spontaneously into the forms of dimers which can further associate into tetramers. The surface of lipid membranes can act as a catalytic platform for the tetramer formation. After incorporation into lipid bilayers, tetrameric structures of AmB function as transmembrane ion channels affecting electrophysiological homeostasis of living cells. Such a mechanism is one of the major causes responsible for severe side effects for patients.

Research methodology

The research planned will be carried out with the use of the molecular spectroscopy and molecular imaging techniques applied to single model lipid membrane objects (liposomes) and single transport protein molecules (“single molecule” approach). In particular, the research planned will be based on FLIM (Fluorescence Lifetime Imaging Microscopy), FCS (Fluorescence Correlation Spectroscopy), Raman imaging microscopy coupled with AFM (Atomic Force Microscopy), CD (Circular Dichroism) spectroscopy and FTIR (Fourier-Transform Infrared) absorption spectroscopy. The detailed research tasks are planned to unveil and understand: (i) molecular mechanisms responsible for self-organization of AmB to dimers and tetramers, in the water phase and in the environments of transport proteins and lipid membranes, (ii) impact of individual AmB molecular organization forms on lipid membrane structure and transmembrane ion transfer, (iii) possibilities of developing of new pharmacological formulas of AmB, based on protein and lipid structures, to prevent formation of tetrameric structures. In parallel, the research will be conducted (iv), based on molecular dynamics calculations of the process of AmB tetramer formation in the lipid membrane environment.

Research project impact

The planned research will result in obtaining precise information on molecular mechanisms responsible for formation of supramolecular structures of AmB, which can be responsible for toxic side effects of the antibiotic. This knowledge will allow designing of chemical modifications of the drug and engineering of new pharmaceutical formulations which retain therapeutic efficacy with substantially reduced toxicity for patients.


Wiesław I. Gruszecki

Rafał Luchowski

Wojciech Grudziński

Monika Zubik-Duda

Renata Welc


Ewa Janik, Joanna Bednarska, Monika Zubik, Karol Sowiński, Rafał Luchowski, Wojciech Grudziński and Wiesław I. Gruszecki

Is It Beneficial for the Major Photosynthetic Antenna Complex of Plants To Form Trimers?

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Joanna Starzyk , Marcin Gruszecki , Krzysztof Tutaj , Rafał Luchowski , Radosław Szlazak , Piotr Waśko , Wojciech Grudziński , Jacek Czub , and Wiesław I. Gruszecki

Self-association of Amphotericin B: Spontaneous Formation of Molecular Structures Responsible for the Toxic Side Effects of the Antibiotic

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Marta Palusińska-Szysz, Agnieszka Zdybicka-Barabas, Małgorzata Cytryńska, Sylwia Wdowiak-Wróbel, Elżbieta Chmiel & Wiesław I. Gruszecki

Analysis of cell surface alterations in Legionella pneumophila cells treated with human apolipoprotein E

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Agnieszka Zdybicka-Barabas, Marta Palusińska-Szysz, Wiesław I. Gruszecki, Paweł Mak, Małgorzata Cytryńska

Galleria mellonella apolipophorin III – an apolipoprotein with anti-Legionella pneumophila activity

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Bożena Pawlikowska-Pawlęga, Lucjan E. Misiak, Anna Jarosz-Wilkołazka, Barbara Zarzyka, Roman Paduch, Antoni Gawron, Wieslaw I. Gruszecki

Biophysical characterization of genistein-membrane interaction and its correlation with biological effect on cells - the case of EYPC liposomes and human erythrocyte membranes

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Project information

Funding body:
Foundation for the Polish Science

Project call:

Project leader:
prof. dr hab. Wiesław Gruszecki

Grant allocation:
3 265 068 PLN

Beginning of the project:

Project status:

Projekt realizowany w programie Team Fundacji na rzecz Nauki Polskiej, współfinansowany przez Unię Europejską w ramach Europejskiego Funduszu Rozwoju Regionalnego.