Dissertation
Study of nanoscale physical properties and intermolecular interactions
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2020
DOI: 10.17077/etd.005676
Abstract
Investigation of physical and chemical properties of nano-dimensional materials has attracted significant attention over the past few decades owing to their increased applications in the fields of pharmaceutics, material science and semiconductors. Characterization of nano-dimensional materials has been an extremely difficult task due to their inherent size limitations. However, the introduction of novel scanning probe techniques such as atomic force microscopy (AFM) has led to advancements in the investigation of a diverse range of properties for materials including the mechanical properties, molecular interactions, electrical properties, viscoelastic properties and surface tension. Herein the dissertation focuses on AFM-based methodology development for the investigation and characterization of crystalline and soft biomaterials at both macro- and nano-dimensions.Understanding structure-property relationship and mechanical properties are important for materials in the nano-dimension to enable rational design and development of drugs, mechanical actuators and semiconductors. It is becoming increasingly clear that the macro- and nano-dimensional materials comprised of same molecules behave differently due the confinement effects at the nanoscale. For an example, we show using AFM nanoindentation that the macro- and nano-dimensional photoresponsive molecular solids of the diarylethene derivative have significantly different Young’s moduli values. The nano-dimensional crystalline wires of diarylethene derivative are 3-times softer than the macro-dimensional molecular crystals. Moreover, as a result of crystal downsizing an individual nanowire underwent accelerated crystalline to amorphous transformation due to photomechanical fatigue where the cooperative nature in an extended crystal structure resisted the fatigue in macro-dimensional diarylethene crystals. Furthermore, we have developed a novel AFM nanoindentation methodology to quantify hardness of nano-dimensional crystals. In particular, we showed using model aspirin nano-dimensional crystalline needles display similar Young’s modulus and hardness values compared to the macro-dimensional aspirin crystals.
Additionally, we have used complementary techniques such as AFM nanoindentation and Brillouin light scattering to investigate the heterogeneity in 3D particle structure of polymeric microgels. The microgels synthesized using polystyrene-co-poly(N-isopropylacrylamide) have a non-uniform distribution in crosslinking densities. The particle synthesis with a low concentration of bisacrylamide crosslinker resulted in a relatively higher crosslinking density near the particle surface as observed by AFM nanoindentation. On the other hand, the particle synthesized with a higher concentration of bisacrylamide crosslinker resulted in a relatively higher crosslinking densities at the microgel core as determined by Brillouin light scattering measurements. This provides additional design space for particle synthesis to be used for drug carrier applications. Furthermore, we showed hepatocarcinoma cells are sensitive to the mechanical properties of microgels and preferentially uptake softer particles. Next, we investigated how the extracellular matrix (ECM) stiffness governs the mechanosensitive endocytosis process. We showed the ECM stiffness was modulated by growing SH-SY5Y cells on substrates of different stiffnesses. With the AFM nanoindentation we showed the ECM stiffness changes depending on the mechanical properties of the substrate on which the cells were plated on. The cells plated on a glass surface were stiffer and up took lower concentration of amyloid beta isoforms. In contrast, the cells plated on soft polyacrylamide gels were softer and up took higher concentration of amyloid beta isoforms. Then the toxicity of oligomeric and fibrillated amyloid beta was assessed based on the ECM elasticity. SH-SY5Y cells plated on soft polyacrylamide gels displayed relatively lower toxicity to oligomeric amyloid beta whereas cells plated on glass surface showed a lower cell viability to a similar oligomeric amyloid beta dosage. Similarly, silica nanoparticle toxicity was assessed and found to be mechanosensitive. AFM nanoindentation and cell viability studies showed that the cells plated on soft surfaces diminish reactive oxygen species silica toxicity in SH-SY5Y neuroblastoma cells. Furthermore, we have studied the use of rigid linkers in AFM-based molecular recognition force spectroscopy to accurately measure protein-ligand interactions. More specifically, the rupture force required to dissociate dihydrofolate reductase (DHFR) enzyme and methotrexate drug molecule complexes were measured with and without the presence of linker molecules on AFM probe and sample surfaces. In here we investigated three different linking scenarios for the methotrexate and DHFR enzyme molecule attachment: direct attachment, attachment through a flexible polyethylene glycol molecules and attachment through rigid dsDNA molecules to respective surfaces. The use of linkers for molecular recognition force spectroscopy improves the accuracy and precision in rupture force measurements compared to the direct attachment while the use of either polyethylene glycol or dsDNA provides similar accuracy and precision. The use of dsDNA linkers found to be beneficial since they provide efficient location of enzyme molecules on the surface while promoting single molecular level measurements. Finally, we have studied how the mesenchymal cells translocate during pulmonary secondary alveolar separation. It was observed that the during elongation the collagen fibers are positioned to provide scaffold for the translocation of cells where the regions that contained fibers have a higher elasticity value. In fibroblast cells platelet-derived growth factor receptor-α and neurophillin-1 genes aid the signaling of mechanosensitive responsiveness to the allow translocate into the regions with increased elasticities.
Overall, the current dissertation discusses the AFM-based method development towards the investigation and characterization of mechanical properties and molecular interactions at both macro- and nano-dimensions. The high spatial and force resolution capabilities of the AFM methods developed herein provide a platform to better understand the factors governing unique properties for material design and processing.
Details
- Title: Subtitle
- Study of nanoscale physical properties and intermolecular interactions
- Creators
- Thiranjeewa Indrachapa Lansakara
- Contributors
- Alexei V Tivanski (Advisor)Leonard R MacGillivray (Committee Member)Lewis L Stevens (Committee Member)Johna Leddy (Committee Member)Elizabeth A Stone (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Chemistry
- Date degree season
- Autumn 2020
- DOI
- 10.17077/etd.005676
- Publisher
- University of Iowa
- Number of pages
- xxx, 313 pages
- Copyright
- Copyright 2020 Thiranjeewa Indrachapa Lansakara
- Language
- English
- Description illustrations
- illustrations (some color)
- Description bibliographic
- Includes bibliographical references (pages 287-313).
- Public Abstract (ETD)
Nano-dimensional materials (that are one billionth of a meter) have recently attracted significant interest for applications in the fields of medicine, pharmaceutics and material science due to their unique physical-chemical properties. Size reduction of a material to the nanoscale can lead to remarkably different properties compared to their bulk counterparts. Hence, it is not feasible to study bulk macroscopic materials and then extrapolate these properties at the nanoscale. Therefore, nanoscale studies that measure, manipulate, and utilize these unique properties are needed
However, due to inherent size limitations of nano-dimensional materials, traditional macroscopic methods cannot be utilized. Atomic force microscopy (AFM) is a versatile microscopic technique which helps us to visualize (i.e. image) and quantify the size and shape of nanomaterials. The AFM is also capable of measuring and applying extremely small forces onto nanomaterials. These enable us to investigate the physical properties such as the elasticity (flexibility) of nanomaterials or develop novel approaches to measure interactions between very few individual molecules. In this context, we investigated the mechanical properties of various materials across different size ranges including polymer nanoparticles, light responsive crystalline and amorphous solids, hydrogels, cells and how to accurately measure interaction forces between a drug molecule bound to an enzyme. This experimental capability of investigating the physical-chemical properties at the nanoscale could enable determination of important factors that govern these properties and potentially allowing us to design novel materials and applications with targeted and unique properties.
- Academic Unit
- Chemistry
- Record Identifier
- 9984036086202771
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