Dokument: Interactive bioinspired polymers to mediate specific and non-specific adhesion
| Titel: | Interactive bioinspired polymers to mediate specific and non-specific adhesion | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=54563 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20201026-105349-9 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Strzelczyk, Alexander Klaus [Autor] | |||||||
| Dateien: |
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| Beitragende: | Jun. Prof. Dr. Schmidt, Stephan [Betreuer/Doktorvater] Prof. Dr. Karg, Matthias [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 540 Chemie | |||||||
| Beschreibung: | This work investigates and utilizes two types of biomolecular motifs that are widely known for their adhesive properties: carbohydrates and catechols. Carbohydrates are involved in almost all adhesive interactions between cells and catechols are the prime molecular groups for biological wet adhesion, e.g. employed by mussels. However, despite the vigorous research activities in the area of carbohydrate and catechol adhesion as well as the high demand for smart and accessible adhesives, synthetic polymers with the nature-equivalent functions and performance were not yet achieved. This is because our current understanding of how the involved specific adhesion processes are mechanistically executed, remain fragmented at best. Therefore, this work quantifies the adhesive interactions of functional catechol and carbohydrate bearing macromolecules.
First, the adhesive properties of catechol-based molecules inspired by adhesive mussel foot proteins were investigated. Therefore, different oligomers with varying combinations and positioning of catechol, tertiary amine, and primary amide on the oligomer backbone were analyzed. The tertiary amines were chosen to study if the cation is responsible for the displacement of salt and water layer by which the adhesion would be amplified. The primary amides were chosen because the mussel foot protein 3 (MFP 3), one of the major constituents of the mussel glue, is rich in primary amides, which might synergize with catechols and amines for strong underwater adhesion. The results of the soft colloidal probe adhesion assay (SCP-RICM) over a pH range from pH 3 to pH 8 provides a quantitative insight to the catechol, amine and/or amide functionalized oligomers on glass surfaces. The combination of amine and catechol synergize to increase adhesion and show dependence towards the positioning of the functional groups in the oligomer sequence. Additionally, the distance between both groups is important. Interestingly, combinations of primary amides with catechol and amine, respectively, show very high adhesion energies at low pH values. Since these combinations are present in the MFP 3 this hints at an intricate interplay of intra- and intermolecular hydrogen bonding of the catechol, amine, and amide groups in the natural sequence, which is controlled by the positioning of the residues along the sequence. The second part is of this thesis is the investigation of carbohydrate mediated specific adhesion between ligand and receptor. Therefore, the well-known model system mannose concanavalin A (ConA) is used. First, carbohydrate bearing polymers with thermoresponsive properties are synthesized. Here, a poly(active ester) is synthesized and functionalized with amine bearing carbohydrates and isopropylamine, where the latter gives thermoresponsive poly(N-isopropyl acrylamide) (PNIPAM) repeating units. The effect of different carbohydrate and PNIPAM ratios and the effect of linkers with varying hydrophilicity, as well as the effects of the coil to globule transition upon temperature increase are analyzed. The polymers are used as temperature-dependent adhesion inhibitors of ConA and Escherichia coli (E. coli) binding to a mannan model surface. Depending on the amount of carbohydrates incorporated into the polymer, changes in the adhesion inhibition can be observed. For low amounts of carbohydrates around 1% or 2%, the inhibitory effect is strongly temperature-dependent but for higher functionalization degrees the cloud point cannot be reached and, therefore, a coil to globule transition takes not place. Interestingly, the inhibition of ConA decreases at elevated temperature whereas for E. coli it increases. This can be explained by the size of the receptors, where, when collapsed, the accessibility of ligands is reduced for the molecularly-sized ConA but increased for the micrometer-sized bacteria. In addition to their inhibitory potential, those polymers are used for adhesion studies to investigate the ligand-receptor interaction at soft/solid interfaces. Here, the SCP-RICM adhesion assay is used to quantify adhesion energies. For this experiment, the polymers are grafted on a poly(ethylene glycol) diacrylamide based hydrogel, the soft colloidal probe (SCP), and the binding protein ConA on a glass surface. Using reflection interference contrast microscopy, the contact areas between polymer functionalized SCPs and protein-coated glass surfaces are measured at different temperatures and adhesion energies are calculated using the Johnson-Kendall-Roberts (JKR) theory. These studies showed that for temperatures above the LCST, the adhesion energies can be switched via temperature change. Additionally, the carbohydrate linker hydrophilicity shows an influence on the adhesion, where the more hydrophilic linker improved the temperature switch, whereas the hydrophobic linker shows no clear temperature dependence. The linker seems to play an important role in the ligand presentation on either the polymer coil or the collapsed globule. Moreover, the adhesion shows a strong hysteresis when cooling back to 20 °C indicating that irreversible non-specific binding may occur at elevated temperatures. Using the JKR model for the SCP adhesion assay requires the determination of the elastic modulus of the SCPs. Therefore, atomic force microscopy (AFM) indentation measurements were done to quantify the elastic moduli of the SCPs. PEG-SCPs are microgels composed of crosslinked bifunctional PEG chains. Non-functionalized PEG microgels, show an increase in elastic modulus with increasing temperature, which is in accordance with De Gennes scaling between the temperature and the elastic modulus for polymer networks in good solvents. When the thermoresponsive polymers are grafted onto the PEG microgels, this behavior changes. Below the LCST an increase in elastic modulus can be seen, owing to the decreasing effective mesh size by the extended PNIPAM chains grafted into the PEG network. When increasing the temperature, the grafted PNIPAM polymers collapse, which results in decreasing elastic moduli, in contrast to the De Gennes scaling. Due to the thermoresponsiveness of the PNIPAM grafts and their collapse at elevated temperature the effective mesh width is increased, which has a strong influence on the elastic modulus. This unexpected change in the elastic modulus may be important for different applications, especially in medical applications, because the stiffness of tissue influences many different cell-cell interactions and communication processes. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Chemie » Organische Chemie und Makromolekulare Chemie | |||||||
| Dokument erstellt am: | 26.10.2020 | |||||||
| Dateien geändert am: | 26.10.2020 | |||||||
| Promotionsantrag am: | 06.08.2020 | |||||||
| Datum der Promotion: | 06.10.2020 |
