FUS (FUsed in Sarcoma) is a protein involved in gene expression. When a mutation occurs, FUS can build up in the cytoplasm and form droplets and fibers because of its prion-like domain. FUS protein...Show moreFUS (FUsed in Sarcoma) is a protein involved in gene expression. When a mutation occurs, FUS can build up in the cytoplasm and form droplets and fibers because of its prion-like domain. FUS protein droplets and fibers are thought to be involved in the development with brain diseases ALS and FTD, so uncovering of the kinetics of these fibers and droplets would aid in medicine development for these diseases. In this thesis, the fiber growth rate as a function of the FUS concentration in the dilute phase surrounding the fiber is measured, using confocal microscopy, by growing the fibers from FUS coated glass beads. This showed that the fiber growth rate in linearly dependent on the FUS concentrations. Secondly, the FUS droplets have been shown to age and harden over time. Here, a tentative attempt is made to quantify this hardening over time using micro rheology. This shows that this hardening indeed happens, but it is not quantifiable yet. These findings are particularly exciting as they suggest that fibril growth rate occurs through a mechanism that is contrary to that predicted from the current paradigm. Thus, this study set the foundation for a more complete physical picture of fibril growth and its alteration by condensates.Show less
In this thesis we present two distinct interferometric set-ups for displacement measuring interferometry in cryogenic Low Energy Electron Microscopy (LEEM), specifically for use in ESCHER, the LEEM...Show moreIn this thesis we present two distinct interferometric set-ups for displacement measuring interferometry in cryogenic Low Energy Electron Microscopy (LEEM), specifically for use in ESCHER, the LEEM at Leiden University. The set-ups are based on: 1. circular polarization and 2. 3x3 fiber couplers to obtain a quadrature measurement. Whilst the 3x3 coupler based set-up is limited by thermal drift and other environmental effects, the circular polarization based method displays a 3\sigma resolution of 1.75 nm, and we provide a framework for further increasing this resolution, including a set of alternate set-ups with slight added complexity but a great potential gain in resolution. Keywords: Displacement, Interferometry, Fiber Couplers, Polarization, LEEM, cryogenic, DMI, Quadrature, Fiber.Show less
