Uhríková D., Hanulová M., Funari S.S., Khusainova R.S., Šeršeň F., Balgavý P.:

The structure of DNA-DOPC aggregates formed in presence of calcium and magnesium ions: A small-angle synchroton X-ray

diffraction study

Biochimica et Biophysica Acta – Biomembranes 1713 (2005) 15-28

Uhríková D., Kučerka N., Teixeira J., Gordeliy V., Balgavý P.:

Structural changes in dipalmitoylphosphatidylcholine bilayer promoted by Ca2+ ions: a small-angle neutron scattering study

Chemistry and Physics of Lipids 155 (2008) 80-89

Bastos M., Silva T., Teixeira V., Nazmi K., Bolscher J.G.M., Funari S.S., Uhríková D.:

Lactoferrin-derived antimicrobial peptide induced a micellar cubic phase in a model membrane system

Biophysical Journal 101 (2011) L20-L22

Pullmannová P., Bastos M., Bai G., Funari S.S., Lacko I., Devínsky F., Teixeira J., Uhríková D.:

The ionic strength effect on the DNA complexation by DOPC - gemini surfactants liposomes

Biophysical Chemistry 160 (2012) 35-45

Uhríková D., Pullmannová P.: Structural Diversity of DNA-Phospholipid Aggregates

In: Liposomes, Lipid Bilayers and Model Membranes. From Basic Research to Application.

Eds.: G. Pabst, N. Kučerka, M.-P. Nieh, J. Katsaras, Boca Raton: CRC Press, 2014, p. 247- 269

ISBN 978-1-4665-0709-8

Kučerka N., Ermakova E., Dushanov E., Kholmurodov K.T., Kurakin S., Želinská K., Uhríková D.: Cation – zwitterionic lipid interactions are affected by the lateral area per lipid

Langmuir 37 (2021) 278-288 

Klacsová M., Čelková A., Búcsi A., Martínez J.C., Uhríková D.: Interaction of GC376, a SARS-CoV-2 Mpro inhibitor, with model lipid membranes.

Colloids and Surfaces B: Biointerfaces 220 (2022) 112918

Liskayová G., Hubčík L., Búcsi A., Fazekaš T., Martínez J. C., Devínsky F., Pisárčik M., Hanulová M., Ritz S., Uhríková D.:

pH-Sensitive N,N-Dimethylalkane-1-amine N-Oxides in DNA Delivery: From Structure to Transfection Efficiency

Langmuir 35 (2019) 13382-13395

Kučerka N., Uhríková D.: Biophysical perspectives of lipid membranes through the optics of neutron and X-ray scattering

In: Characterization of Biological Membranes: Structure and Dynamics.

Berlin: De Gruyter, 2019. p. 1-42, ISBN 9783110544657

Královič-Kanjaková N., Asi Shirazi A., Hubčík L., Klacsová M., Keshavarzi A., Martínez J.C., Combet S., Teixeira J., Uhríková D.:

Polymyxin B - enriched exogenous lung surfactant: thermodynamics and structure

Langmuir 40 (2024) 6747-6861

Wettig S.D., Verrall R.E., Foldvari M.: Gemini Surfactants: A New Family of Building Blocks for Non

Viral Gene Delivery Systems. Curr. Gene Ther. 8 (2008) 9-23

referred papers:

Uhríková D., Rapp G., Balgavý P.: Condensed Lamellar Phase in Ternary DNA-DLPC-Cationic Gemini

Surfactant System: A Small-Angle Synchrotron X-Ray Diffraction Study

Bioelectrochemistry 58 (2002) 87-95

Uhríková D., Hanulová M., Funari S.S., Lacko I., Devínsky F., Balgavý P.: The structure of DNA - DPLC

cationic gemini surfactant aggregates: a small angle synchotron X-ray diffraction study

Biophysical Chemistry 111 (2004)197-204

Uhríková D., Zajac I., Dubničková M., Pisárčik M., Funari S.S., Rapp G., Balgavý P.: Interaction of gemini

surfactants butane-1,4-diyl-bis-(alkyldimethylammonium bromide) with DNA

Colloids and Surfaces B – Biointerfaces 42 (2005) 59-68

Risselada H.J., Bubnis G., Grubmuller H.: Expansion of the fusion stalk and its implication for biological

membrane fusion. Proc. Natl. Acad. Sci USA 111(2014) 11043-11048

referred paper:

Uhríková D., Kučerka N., Teixeira J., Gordeliy V., Balgavý P.:

Structural changes in dipalmitoylphosphatidylcholine bilayer promoted by Ca2+ ions: a small-angle neutron scattering study

Chemistry and Physics of Lipids 155 (2008) 80-89

Xu Y., Kuhlmann J., Brennich M., Komorowski K., Jahn R., Steinem C., Salditt T.:

Biochimica et Biophysica Acta - Biomembranes 1860 (2018) 578

referred paper:

Kučerka N., Dushanov E., Kholmurdorov K.T., Katsaras J., Uhríková D.: Calcium and zinc differentially affect the structure of lipid membranes

Langmuir 33 (2017) 3134-3141

Canadas O., Olmeda B., Alonso A., Pérez-Gil, J.:

International Journal of Molecular Sciences 21 (2020) 3708

referred paper:

Kolomazník M., Liskayová G., Královič N., Hubčík L., Uhríková D., Čalkovská A.:

The perturbation of pulmonary surfactant by bacterial lipopolysaccharide and its reversal by polymyxin B: Function and structure

International Journal of Molecular Sciences 19 (2018) 1964

Antoniou A.I., Giofré S., Seneci P., Passarella D., Pellegrino S.:

Stimulus-responsive liposomes for biomedical applications

Drug Discovery Today 26 (2021) 1794 - 1824

referred paper:

Liskayová G., Hubčík L., Búcsi A., Fazekaš T., Martínez J. C., Devínsky F., Pisárčik M., Hanulová M., Ritz S., Uhríková D.:

pH-Sensitive N,N-Dimethylalkane-1-amine N-Oxides in DNA Delivery: From Structure to Transfection Efficiency

Langmuir 35 (2019) 13382-13395

VEGA 1/0916/16

Non-lamellar lipidic mesophases in target drugs delivery, principal investigator D. Uhríková

The aim of the project is to study an encapsulation of hydrophilic macromolecules of drugs into water nanotubules

of non lamellar liquid-crystalline mesophases (cubosomes, hexosomes) as targeted delivery systems.

Nanocarriers will be prepared as a mixture of amphiplilic additives and either glycerol monooleate or neutral

phospholipids forming w/o dispersions. Additives, N,N-dimethyl-N-alkanamine-N-oxides, fatty acids or alifatic

alcohols will be used to modulate the diameter of water tubules of non lamellar structures. The nanocarriers are

designed for short one-strand nucleic acids (NA) or antimicrobial peptides (AMP). We also intend to follow the

system’s kinetics related to drugs binding and release, in addition to its structure and physico-chemical

properties.Transfection experiments for selected nanocarriers are proposed.

VEGA 1/0223/20

Lipid bilayer in pulmonary surfactant models: interactions and targeting drug delivery, principal investigator D. Uhríková

The project proposes biophysical study of pulmonary surfactant (PS)-drug systems with the aim to employ

exogenous PS (EPS) as a drug carrier for specific drugs. Peptid based antibiotics (Polymyxin B, cathelicidin

LL-37), steroids (cholesterol, budesonide) and antiviral agents (zanamivir, oseltamivir) are of interest in combined

therapy natural EPS/drug. Hydrophilic/lipophilic composition of the drugs determines their intercalation either into

PS phospholipid bilayer or in the bilayer polar headgroup region. PS model systems will be prepared from

mixtures of lipids (with/without SP-B, SP-C proteins) mimicking endogenous PS. The aim of the study is to

examine link between structure and its changes vs. functionality of EPS at normal and pathological conditions.

Curosurf, natural exogenous PS will be used as an “etalon” for the comparison. Toxicity of EPS/drug systems will

be tested in vitro. The intriguing question namely is: How much can synthetic EPS mimic therapeutically used Cur

at different conditions?

APVV - 17-0250

Pulmonary surfactant as a modulator of body's response to endotoxin exposure: effects and mechanisms

A. Čalkovská, Jessenius Faculty of Medicine, Martin, CU Bratislava, principal investigator

D. Uhríková, Faculty of Pharmacy, CU Bratislava, principal investigator of participating research organization

The pulmonary surfactant is a lipoprotein complex present in the alveoli and airways, where it reduces surface

tension and prevents the lung collapse. The pulmonary surfactant may under certain circumstances be

inactivated by endotoxin (lipopolysaccharide, LPS) from Gram-negative bacteria membranes, which may lead to

respiratory failure. The aim of the project is to contribute to the understanding of the role of surfactant in the local

defensive mechanisms of the lungs. The effect of LPS on the respiratory system will be studied in a complex

way, by in vivo modeling (on animals), by ex vivo testing on smooth airway muscle and in alveolar epithelial cells

cultures. Mechanisms of surfactant vs. LPS interaction will be studied in vitro in a pulsating bubble

surfactometer, changes of fluidity by fluorescent spectroscopy and structural changes by small angle (SAXD)

and wide angle (WAXD) X-ray diffraction. The visualization of the structural changes at cellular level will be

performed by X-ray cryo-tomography. The results obtained by wide range of experimental methods allow to

create a holistic picture of the effect of endotoxin on the respiratory system, its interaction with surfactant, and

new treatment options. The project yields in original findings regarding the potential use of exogenous surfactant

in LPS-induced inflammation. The relationship between surfactant and endotoxin will be of particular relevance

to clinical practice, as well as the evidence that surfactant can serve as a carrier of drugs with anti-inflammatory,

antioxidant or antimicrobial properties directly to the respiratory system.

VEGA 1/0305/24

Exogenous pulmonary surfactant for the delivery of antiviral drugs: interactions and structural stability

principal investigator D. Uhríková

The project proposes a biophysical study of antiviral/exogenous pulmonary surfactant (EPS) systems to

determine the drug binding capacity of EPS while maintaining the structural stability and functionality of the

carrier. A wide range of experimental methods will be applied. The dual approach, using the EPS model

composed of a mixture of lipids (with/without PS-specific proteins) and the therapeutically used Curosurf, will

highlight the role of proteins. We will focus on antivirals targeted at genetic material and life cycle enzymes of the

SARS-CoV-2 virus (remdesivir, molnupiravir, nirmatrelvir, and peptidomimetic protease inhibitors). Recent

research suggests a potentially significant role for the human antimicrobial peptide LL-37 in the fight against

coronavirus. We will investigate the interactions and structural changes in EPS/LL-37 with the virus spike protein

S. The main motivation of the study is to evaluate the feasibility of using EPS as a carrier for antivirals and the

possible limitations.

APVV SK - PT - 18 - 0032

Phospholipid membranes as a target of antimicrobial agents

project of bilateral collaboration Slovak Republic - Portugal, principal investigator SR: D. Uhríkova,

The emergence of bacterial pathogens with acquired resistance to most antibiotics is a growing medical

concern, urging the discovery of new, safe and effective antimicrobial agents, with alternative mechanisms

of action that do not easily induce resistance. One proposed strategy, representing a new paradigm in

antibiotic therapy, is the use of bacterial membranes as therapeutic target.

The aim of the project is the unveiling of the mechanism(s) of antimicrobial activity of antimicrobial

peptides and peptide based antibiotics against various pathogens, using model membrane studies.

The project bridges strong biophysical and computational approaches, and the information obtained from

structural studies will be combined with data from thermodynamic experiments and information from

molecular dynamics simulation. The benefit of the collaboration, aside from sharing experimental

techniques, is the complementary knowledge and experience of the team in the field.