Continuous Flow Atomic Force Microscopy Imaging Reveals Fluidity and Time-Dependent Interactions of Antimicrobial Dendrimer with Model Lipid Membranes
- Tania Kjellerup Lind ,
- Paulina Zielińska ,
- Hanna Pauliina Wacklin ,
- Zofia Urbańczyk-Lipkowska , and
- Marité Cárdenas
Abstract

In this paper, an amphiphilic peptide dendrimer with potential applications against multi-resistant bacteria such as Staphylococcus aureus was synthesized and studied on model cell membranes. The combination of quartz crystal microbalance and atomic force microscopy imaging during continuous flow allowed for in situ monitoring of the very initial interaction processes and membrane transformations on longer time scales. We used three different membrane compositions of low and high melting temperature phospholipids to vary the membrane properties from a single fluid phase to a pure gel phase, while crossing the phase coexistence boundaries at room temperature. The interaction mechanism of the dendrimer was found to be time-dependent and to vary remarkably with the fluidity and coexistence of liquid–solid phases in the membrane. Spherical micelle-like dendrimer–lipid aggregates were formed in the fluid-phase bilayer and led to partial solubilization of the membrane, while in gel-phase membranes, the dendrimers caused areas of local depressions followed by redeposition of flexible lipid patches. Domain coexistence led to a sequence of events initiated by the formation of a ribbon-like network and followed by membrane solubilization via spherical aggregates from the edges of bilayer patches. Our results show that the dendrimer molecules were able to destroy the membrane integrity through different mechanisms depending on the lipid phase and morphology and shed light on their antimicrobial activity. These findings could have an impact on the efficacy of the dendrimers since lipid membranes in certain bacteria have transition temperatures very close to the host body temperature.
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- Mudassar Mumtaz Virk, Benedikt Hofmann, Erik Reimhult. Formation and Characteristics of Lipid-Blended Block Copolymer Bilayers on a Solid Support Investigated by Quartz Crystal Microbalance and Atomic Force Microscopy. Langmuir 2019, 35 (3) , 739-749. https://doi.org/10.1021/acs.langmuir.8b03597
- Arielle C. Mensch, Joseph T. Buchman, Christy L. Haynes, Joel A. Pedersen, Robert J. Hamers. Quaternary Amine-Terminated Quantum Dots Induce Structural Changes to Supported Lipid Bilayers. Langmuir 2018, 34 (41) , 12369-12378. https://doi.org/10.1021/acs.langmuir.8b02047
- Kai Lv, Li Zhang, Wensheng Lu, and Minghua Liu . Control of Supramolecular Chirality of Nanofibers and Its Effect on Protein Adhesion. ACS Applied Materials & Interfaces 2014, 6 (21) , 18878-18884. https://doi.org/10.1021/am504702p
- Guilherme Colherinhas and Eudes Fileti . Molecular Dynamics Study of Surfactant-Like Peptide Based Nanostructures. The Journal of Physical Chemistry B 2014, 118 (42) , 12215-12222. https://doi.org/10.1021/jp5082593
- Tania Kjellerup Lind, Marité Cárdenas, and Hanna Pauliina Wacklin . Formation of Supported Lipid Bilayers by Vesicle Fusion: Effect of Deposition Temperature. Langmuir 2014, 30 (25) , 7259-7263. https://doi.org/10.1021/la500897x
- Tianfu Li, Naimin Shao, Yuntao Liu, Jingjing Hu, Yu Wang, Li Zhang, Hongli Wang, Dongfeng Chen, and Yiyun Cheng . Poly(amidoamine) and Poly(propyleneimine) Dendrimers Show Distinct Binding Behaviors with Sodium Dodecyl Sulfate: Insights from SAXS and NMR Analysis. The Journal of Physical Chemistry B 2014, 118 (11) , 3074-3084. https://doi.org/10.1021/jp412660p
- Kathleen W. Swana, Ramanathan Nagarajan, Terri A. Camesano. Atomic Force Microscopy to Characterize Antimicrobial Peptide-Induced Defects in Model Supported Lipid Bilayers. Microorganisms 2021, 9 (9) , 1975. https://doi.org/10.3390/microorganisms9091975
- Marta Sowińska, Monika Szeliga, Maja Morawiak, Elżbieta Ziemińska, Barbara Zabłocka, Zofia Urbańczyk-Lipkowska. Peptide Dendrimers with Non-Symmetric Bola Structure Exert Long Term Effect on Glioblastoma and Neuroblastoma Cell Lines. Biomolecules 2021, 11 (3) , 435. https://doi.org/10.3390/biom11030435
- Josefine Eilsø Nielsen, Sylvain François Prévost, Håvard Jenssen, Reidar Lund. Impact of antimicrobial peptides on E. coli -mimicking lipid model membranes: correlating structural and dynamic effects using scattering methods. Faraday Discussions 2021, 30 https://doi.org/10.1039/D0FD00046A
- K.G. Schaefer, A.E. Pittman, F.N. Barrera, G.M. King. Atomic force microscopy for quantitative understanding of peptide-induced lipid bilayer remodeling. Methods 2020, 119 https://doi.org/10.1016/j.ymeth.2020.10.014
- Maja Morawiak, Magdalena Stolarska, Maciej Cieślak, Zofia Urbanczyk‐Lipkowska. Interactions of rationally designed small peptide dendrons functionalized with valine or sinapic acid with α‐helix and β‐sheet structures of poly‐ l ‐lysine and poly‐ l ‐glutamic acid. Peptide Science 2020, 112 (3) https://doi.org/10.1002/pep2.24155
- Luke A. Clifton, Richard A. Campbell, Federica Sebastiani, José Campos-Terán, Juan F. Gonzalez-Martinez, Sebastian Björklund, Javier Sotres, Marité Cárdenas. Design and use of model membranes to study biomolecular interactions using complementary surface-sensitive techniques. Advances in Colloid and Interface Science 2020, 277 , 102118. https://doi.org/10.1016/j.cis.2020.102118
- Søren Wedel Svenningsen, Rikki Franklin Frederiksen, Claire Counil, Mario Ficker, Jørgen J. Leisner, Jørn Bolstad Christensen. Synthesis and Antimicrobial Properties of a Ciprofloxacin and PAMAM-dendrimer Conjugate. Molecules 2020, 25 (6) , 1389. https://doi.org/10.3390/molecules25061389
- Arielle C. Mensch, Eric S. Melby, Elizabeth D. Laudadio, Isabel U. Foreman-Ortiz, Yongqian Zhang, Alice Dohnalkova, Dehong Hu, Joel A. Pedersen, Robert J. Hamers, Galya Orr. Preferential interactions of primary amine-terminated quantum dots with membrane domain boundaries and lipid rafts revealed with nanometer resolution. Environmental Science: Nano 2020, 7 (1) , 149-161. https://doi.org/10.1039/C9EN00996E
- Josefine Eilsø Nielsen, Tania Kjellerup Lind, Abdullah Lone, Yuri Gerelli, Paul Robert Hansen, Håvard Jenssen, Marité Cárdenas, Reidar Lund. A biophysical study of the interactions between the antimicrobial peptide indolicidin and lipid model systems. Biochimica et Biophysica Acta (BBA) - Biomembranes 2019, 1861 (7) , 1355-1364. https://doi.org/10.1016/j.bbamem.2019.04.003
- Bruno Amorim-Carmo, Alessandra Daniele-Silva, Adriana M. S. Parente, Allanny A. Furtado, Eneas Carvalho, Johny W. F. Oliveira, Elizabeth C. G. Santos, Marcelo S. Silva, Sérgio R. B. Silva, Arnóbio A. Silva-Júnior, Norberto K. Monteiro, Matheus F. Fernandes-Pedrosa. Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin. International Journal of Molecular Sciences 2019, 20 (3) , 623. https://doi.org/10.3390/ijms20030623
- Débora Fretes Argenta, Silvia Maria Martelli, Thiago Caon. Dendrimer as a platform for drug delivery in the skin. 2019,,, 331-367. https://doi.org/10.1016/B978-0-12-818433-2.00010-8
- Josefine Eilsø Nielsen, Victoria Ariel Bjørnestad, Reidar Lund. Resolving the structural interactions between antimicrobial peptides and lipid membranes using small-angle scattering methods: the case of indolicidin. Soft Matter 2018, 14 (43) , 8750-8763. https://doi.org/10.1039/C8SM01888J
- N. Ashwanikumar, Justin S. Plaut, Barmak Mostofian, Siddharth Patel, Peter Kwak, Conroy Sun, Kerry McPhail, Daniel M. Zuckerman, Sadik C. Esener, Gaurav Sahay. Supramolecular self assembly of nanodrill-like structures for intracellular delivery. Journal of Controlled Release 2018, 282 , 76-89. https://doi.org/10.1016/j.jconrel.2018.02.041
- Xingran Zhang, Zhiwei Wang, Chuyang Y. Tang, Jinxing Ma, Mingxian Liu, Meng Ping, Mei Chen, Zhichao Wu. Modification of microfiltration membranes by alkoxysilane polycondensation induced quaternary ammonium compounds grafting for biofouling mitigation. Journal of Membrane Science 2018, 549 , 165-172. https://doi.org/10.1016/j.memsci.2017.12.004
- Marianna Mamusa, Leopoldo Sitia, Francesco Barbero, Angels Ruyra, Teresa Díaz Calvo, Costanza Montis, Ana Gonzalez-Paredes, Grant N. Wheeler, Christopher J. Morris, Michael McArthur, Debora Berti. Cationic liposomal vectors incorporating a bolaamphiphile for oligonucleotide antimicrobials. Biochimica et Biophysica Acta (BBA) - Biomembranes 2017, 1859 (10) , 1767-1777. https://doi.org/10.1016/j.bbamem.2017.06.006
- Jonas Stenbæk, David Löf, Peter Falkman, Bo Jensen, Marité Cárdenas. An alternative anionic bio-sustainable anti-fungal agent: Investigation of its mode of action on the fungal cell membrane. Journal of Colloid and Interface Science 2017, 497 , 242-248. https://doi.org/10.1016/j.jcis.2017.03.018
- David Alsteens, Hermann E. Gaub, Richard Newton, Moritz Pfreundschuh, Christoph Gerber, Daniel J. Müller. Atomic force microscopy-based characterization and design of biointerfaces. Nature Reviews Materials 2017, 2 (5) https://doi.org/10.1038/natrevmats.2017.8
- Cigdem Yucel Falco, Javier Sotres, Ana Rascón, Jens Risbo, Marité Cárdenas. Design of a potentially prebiotic and responsive encapsulation material for probiotic bacteria based on chitosan and sulfated β-glucan. Journal of Colloid and Interface Science 2017, 487 , 97-106. https://doi.org/10.1016/j.jcis.2016.10.019
- Ugir H. Sk. Nanosize Dendrimers: Potential Use as Carriers and Antimicrobials. 2017,,, 323-355. https://doi.org/10.1016/B978-0-323-52733-0.00012-4
- Zahoor Parry, Rajesh Pandey. Emerging Aspects in Dendrimer Research. 2016,,, 189-209. https://doi.org/10.1201/9781315366005-12
- Marianna Mamusa, Claudio Resta, Francesco Barbero, Davide Carta, Doroty Codoni, Kostas Hatzixanthis, Michael McArthur, Debora Berti. Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials. Colloids and Surfaces B: Biointerfaces 2016, 143 , 139-147. https://doi.org/10.1016/j.colsurfb.2016.03.031
- Tania K. Lind, Marité Cárdenas. Understanding the formation of supported lipid bilayers via vesicle fusion—A case that exemplifies the need for the complementary method approach (Review). Biointerphases 2016, 11 (2) , 020801. https://doi.org/10.1116/1.4944830
- T.K. Lind, L. Darré, C. Domene, Z. Urbanczyk-Lipkowska, M. Cárdenas, H.P. Wacklin. Antimicrobial peptide dendrimer interacts with phosphocholine membranes in a fluidity dependent manner: A neutron reflection study combined with molecular dynamics simulations. Biochimica et Biophysica Acta (BBA) - Biomembranes 2015, 1848 (10) , 2075-2084. https://doi.org/10.1016/j.bbamem.2015.05.015
- Tania Lind, Piotr Polcyn, Paulina Zielinska, Marité Cárdenas, Zofia Urbanczyk-Lipkowska. On the Antimicrobial Activity of Various Peptide-Based Dendrimers of Similar Architecture. Molecules 2015, 20 (1) , 738-753. https://doi.org/10.3390/molecules20010738
- Magali Deleu, Jean-Marc Crowet, Mehmet N. Nasir, Laurence Lins. Complementary biophysical tools to investigate lipid specificity in the interaction between bioactive molecules and the plasma membrane: A review. Biochimica et Biophysica Acta (BBA) - Biomembranes 2014, 1838 (12) , 3171-3190. https://doi.org/10.1016/j.bbamem.2014.08.023
- R. Bhattacharya, Subbarao Kanchi, Roobala C., A. Lakshminarayanan, Oliver H. Seeck, Prabal K. Maiti, K. G. Ayappa, N. Jayaraman, J. K. Basu. A new microscopic insight into membrane penetration and reorganization by PETIM dendrimers. Soft Matter 2014, 10 (38) , 7577-7587. https://doi.org/10.1039/C4SM01112K
- Yiyun Cheng, Libo Zhao, Tianfu Li. Dendrimer–surfactant interactions. Soft Matter 2014, 10 (16) , 2714. https://doi.org/10.1039/c3sm53180e



