Antimicrobial polymers and surfaces: theoretical and experimental studies

Abstract: Theoretical studies performed in this thesis aimed to prepare a molecular dynamics (MD) simulation model for an antimicrobial diamine synthetic mimics of antimicrobial peptides (SMAMP) homopolymer in a united-atom GROMOS 54A7 force field [1,2]. These studies focused mainly on computing the atomic point charges of a model molecule consisting of three repeat units of a diamine poly(oxanorbornene) SMAMP using Bader analysis [3] and electrostatic potential (ESP) fitting schemes [4,5]. For this purpose, MD simulations were carried out using the GROMACS software [6,7] applying the GROMOS 54A7 force field, and density functional theory (DFT) calculations with the Perdew–Burke-Ernzerhof (PBE) functional were carried out using GPAW [8,9]. For the validation of this model, a comparison was carried out between the potential energy landscapes experienced in the classical force field model (GROMOS54A7) using the newly computed ESP charges and originally implemented van der Waals parameters and the potential energy landscapes in the reference ab initio DFT calculations. These landscapes were computed when a single water molecule was placed at a varying offset from the neutral diamine SMAMP at different adsorption positions. Thus, the applied partial charges and the van der Waals parameters of diamine SMAMP were validated.
The results showed that the calculated ESP-fitted charges and Bader charges were in qualitative agreement. The ESP-fitted charges of the neutral diamine SMAMP were comparable to the partial charges of the lysine amino acid, which have already been parameterized and implemented in GROMOS 54A7 forced field [1,2,10]. Fluctuations of the values of the charges obtained by changing the applied conformation of diamine SMAMP were also observed. From the energy landscape maps, an overall general good agreement was achieved between the classical force field and DFT calculations. Thus, the ESP-fitted charges and van der Waals parameters of the neutral diamine SMAMP presented here can describe its interaction with liquid water efficiently. Accordingly, it is expected that the ESP-fitted charges and van der Waals parameters presented here would also provide a valid description of the interaction of diamine SMAMP with biomolecules in aqueous solutions [11]. Consequently, this model will enable targeted theoretical studies of the antimicrobial mechanism of action of SMAMPs with various biomolecules via simulations, specifically simulations with the previously reported complex bacterial membranes of the Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria [12] that have been studied using the same force field.
Experimental studies performed in this thesis aimed to prepare surfaces that contain the antimicrobial propyl SMAMP homopolymer (the second SMAMP homopolymer that was used in this study after the diamine SMAMP) and/or the protein-repellent polysulfobetaines (PSB) and to study their potential to prevent protein and bacterial adhesion, the first steps in biofilm formation. These polymers were immobilized on micro- and nano-patterned structures obtained by the colloidal lithography (CL) technique (structure patterns spacings: 200 nm, 500 nm, 1 µm and 2 µm) [13–15]. The physical properties of the fabricated surfaces were investigated using atomic force microscopy (AFM) and contact angle measurements. Their protein resistivity was studied by surface plasmon resonance (SPR) spectroscopy. Spray tests were used to study their antimicrobial activity against Gram-negative E. coli bacteria. The growth of human gingival mucosal keratinocytes on the fabricated surfaces was analyzed with the Alamar blue assay, optical microscopy, and live-dead staining. Furthermore, for the fabricated bifunctional surfaces, additional quantitative nanomechanical measurements were performed using atomic force microscopy (QNM-AFM) to obtain their local elastic moduli.
The results showed the influence of the underlying structure itself on the reduction of the protein and bacterial adhesion. At the small spacings, the structured surfaces had an enhancement in their cell adhesion and antimicrobial activity. Additionally, this effect increased when the patterned surfaces were functionalized with a cell-adhesive polycation polymer, such as propyl SMAMP. The structured surfaces functionalized with propyl SMAMP had improved antimicrobial activity, a reduction of unspecific protein adhesion, and improved cellular adhesion in comparison to the unstructured functionalized surfaces with the same polymer. Therefore, structured surfaces functionalized with adhesive polymers such as SMAMPs could be promising candidates to enhance tissue integration on implants [14]. QNM-AFM studies also showed that the obtained bifunctional surfaces were quite stiff due to the high elastic modules of the underlying substrate. These bifunctional surfaces had a reduced antimicrobial activity compared to softer bifunctional surfaces fabricated by the microcontact printing (µCP) technique [16]. The CL-fabricated surfaces also could not fully achieve the required simultaneous quantitative antimicrobial activity and protein repellency. However, the cell compatibility of the CL-fabricated surfaces was maintained at all the tested spacings [15]. The optimum spacing of these CL-fabricated surfaces for bioactivity was found to be in the range from 500 nm to 1 µm [13,15], and a significant reduction of antimicrobial activity was observed at the larger (2 µm) spacing [15].

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13. Vöhringer, M.; Hartleb, W.; Lienkamp, K. Surface Structuring Meets Orthogonal Chemical Modifications: Toward a Technology Platform for Site-Selectively Functionalized Polymer Surfaces and BioMEMS. ACS Biomater. Sci. Eng. 2017, 3, 909–921, doi:10.1021/acsbiomaterials.7b00140.
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Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2021

Klassifikation und Themen

• Schlagwort: Antimicrobial polymers

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: El Sayed Mahmoud, Sarah Mohamed
• Beteiligte Personen und Organisationen: Lienkamp, Karen ; Albert-Ludwigs-Universität Freiburg. Fakultät für Angewandte Wissenschaften

Weitere Informationen

• DOI: 10.6094/UNIFR/193931
• URN: urn:nbn:de:bsz:25-freidok-1939315
• Rechteinformation: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:36 MESZ