Supported Lipid Membranes and Their Use for the Characterization of Biological Nanoparticles
Doctoral thesis, 2020
To investigate SLBs, we combined confocal microscopy with microfluidics to identify the mechanisms by which lipid vesicles are spontaneously converted into various types of planar membranes on a multitude of surfaces (Paper I) and found that most of the studied materials can support lipid film formation. In the context of SLB formation, specific focus was put on using total internal reflection fluorescence (TIRF) microscopy to monitor the kinetics of vesicle adsorption, rupture and spreading of individual SLB patches on glass (Paper II), revealing that the SLB formation process was driven by the autocatalytic growth and merger of multiple small SLB patches at appreciably high vesicle coverage. TIRF was also successfully employed to monitor lipid-enveloped drug permeation through an SLB formed on a mesoporous silica thin film (Paper III). The insights gained from investigating SLBs was also used for in depth characterization of BNPs using the surface-based flow-nanometry method, allowing for independent determination of size and fluorescence emission of individual BNPs tethered to a laterally fluid SLB formed on the floor of a microfluidic channel. This way we could demonstrate that the fluorescence emission from lipophilic dyes depends in a non-trivial way on nanoparticle size, and varies significantly between the different types of BNPs (Paper IV). The flow-nanometry concept was also used to elucidate the effect of vesicle size on their diffusivity on the SLB in the limit of few tethers (Paper V).
The insights gained in this thesis work on lipid self-assembly at different surfaces and the possibility to use SLBs on silica for in-depth characterization of BNPs demonstrate this as a promising approach in the field of single nanoparticle analytics, which in future work will be possible to extend into a novel means to probe interactions between BNPs and cell-membrane mimics representing a near-native situation.
supported lipid bilayer
Chalmers, Physics, Biological Physics
Molecular Lipid Films on Microengineering Materials
Langmuir,; Vol. 35(2019)p. 10286-10298
Spatiotemporal Kinetics of Supported Lipid Bilayer Formation on Glass via Vesicle Adsorption and Rupture
Journal of Physical Chemistry Letters,; Vol. 9(2018)p. 5143-5149
Paul Joyce, Silver Jõemetsa, Simon Isaksson, and Fredrik Höök Investigating Poorly Water-Soluble Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica
Independent Size and Fluorescence Emission Determination of Individual Biological Nanoparticles Reveals that Lipophilic Dye Incorporation Does Not Scale with Particle Size
Langmuir,; Vol. 36(2020)p. 9693-9700
Silver Jõemetsa, Erik Olsén, Adrián González Rodríguez, Paul Joyce, and Fredrik Höök Effects of Vesicle Size on Their Diffusivity when Linked to a Supported Lipid Bilayer
In this work, I have investigated these small particles and their interactions with simplified cell membrane models. Specifically, I have studied how these model membranes react with common materials used in implants and as drug-carriers, but also how the membranes interacted with relevant drugs themselves. It became apparent, that the model membrane system can aid the development and testing of future more advanced means of drug-delivery. Secondly, I studied small virus-like particles to help characterize their size and membrane properties for further usage in diagnostics and drug discovery applications. This was all made possible by advanced microscopy techniques and small microfluidic devices.
It is my hope that the insights gained from this research will bring us one step closer to discovering the early stages of disease progression and to better address debilitating diseases through more efficient delivery of new drugs.
Other Physics Topics
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4702
Chalmers University of Technology
Kollektorn, MC2, Kemivägen 9, Chalmers
Opponent: Jonas Tegenfeldt, Lund University, Sweden