Biological cells, the basic building blocks of all life forms, are surrounded by a lipid membrane. More than half of the membrane is occupied by membrane proteins, which can regulate the cell... Show moreBiological cells, the basic building blocks of all life forms, are surrounded by a lipid membrane. More than half of the membrane is occupied by membrane proteins, which can regulate the cell functionality through specific arrangements. To regulate the arrangements several proteins have to work together. In addition to direct forces, there exists an indirect force between the proteins, which stems from their deformation of the membrane and contributes to their self-organization. Since the actual membrane is very crowded and proteins are too tiny and complex to measure this interaction, in this thesis we used a model system consisting of lipid membranes and solid particles to study the deformation-mediated interaction. We experimentally confirmed for the first time that, unlike many known forces, this deformation-mediated interaction is not additive, i.e. the strength and range of three (or more) deformations cannot be obtained by simple addition of the interactions between pairs of deformations. We found that the interaction weakens with increasing number of membrane-deforming particles and that the particle become less ordered. We investigated deformations in both directions of the membrane and found that the interaction can be both repulsive and attractive, and furthermore depends on the shape of the deformation. This thesis helps to better understand the organization of proteins that deform cellular membranes. Show less
Detecting nanoscopic objects plays an important role in nanoscience in particular, in the rapidly growing field of nanobiology. The forebear to modern super-resolution microscopy for single... Show moreDetecting nanoscopic objects plays an important role in nanoscience in particular, in the rapidly growing field of nanobiology. The forebear to modern super-resolution microscopy for single molecule investigation, is fluorescence microscopy. Fluorescence as a contrast mechanism, however, brings several restrictions. These include (1) the use of the label itself, which may introduce artifacts to the interpretation, (2) the limited photoemission caused by photobleaching and photoblinking as well as (3) low bandwidth of the emission. Fluorescence-free alternatives are thus highly desirable to overcome these limitations. Optical detection of individual proteins with high bandwidth holds great promise for understanding important biological processes on the nanoscale. In this thesis, we investigate label-free optoplasmonic detection of single proteins and particles in motion. Analysing the data provide information about the hydrodynamic volume of the diffuser and interaction such as binding events. Show less
A single self-assembled semiconductor quantum dot in a high-finesse optical microcavity - the subject of this thesis - is an interesting quantum-mechanical system for future quantum applications.... Show moreA single self-assembled semiconductor quantum dot in a high-finesse optical microcavity - the subject of this thesis - is an interesting quantum-mechanical system for future quantum applications. For instance, this system allows trapping of an extra electron and thus can serve as a spin quantum memory, or enables high-fidelity and high-rate single-photon production. We investigate several aspects in this thesis:First, the operation and manipulation of the system is achieved using resonant laser spectroscopy. This requires filtering out of the relatively strong excitation laser, which is often done using the cross-polarization technique. This approach, however, is complicated in optical setups by spin-orbit coupling of light at the beamsplitter. We experimentally firstly explore this effect in a cryogenic optical microscope and demonstrate its importance for quantum dot based single photon sources. Next, we develop a unique setup with a cold permanent magnet and firstly realise trapping of a single electron in our particular quantum dot - cavity devices and show spin control. Then we show how true single photons from our device can be used to create novel quantum states of light. First, we investigate theoretically single photon addition to coherent laser light including several experimental imperfections - we find an universal behaviour of the photon correlation function. Finally, we demonstrate entanglement of several consecutive photons by repeatedly using Hong-Ou-Mandel quantum interference of single photons with a photon quantum memory in the form of an optical delay loop. We show that this results in quantum states of light that have Poissonian photon statistics like laser light - therefore we call them artificial coherent states - but also that they are more complicated than ordinary coherent states and contain multi-photon quantum entanglement in the form of linear cluster states, a potential resource for universal quantum computing. Show less
The first direct detection of gravitational waves opened the possibility of mapping the Universe via this new and independent messenger. Indeed, during their propagation, gravitational waves pick... Show moreThe first direct detection of gravitational waves opened the possibility of mapping the Universe via this new and independent messenger. Indeed, during their propagation, gravitational waves pick up information about the spacetime as they are affected by its expansion and by the matter structures along the propagation path. The aim of this Thesis is to investigate which cosmological information is accessible from a gravitational wave detection, with a specific interest in the late time Universe. Show less
Mechanical metamaterials are carefully engineered materials whose properties are controlled by their structure, not by their composition, which allows using metamaterials to study and control... Show moreMechanical metamaterials are carefully engineered materials whose properties are controlled by their structure, not by their composition, which allows using metamaterials to study and control physical effects in detail. Here we develop metamaterials to study the sequential, complex response of frustrated materials that are cyclically driven. In particular, we focus on metamaterials that act as collections of hysteretic, bistable elements called hysterons. We create hysterons in metamaterials by using local frustration at defects and by using a competition between two global, incompatible deformations modes. We show how we can tune these hysterons, both by rational design and by using spatial gradients in the mechanical driving. Then we show that collectively, our samples exhibit complex transition pathways, including those with avalanches, and study the role of hysteron interactions. Finally, we explore how to control the frustration by local defects in so-called monoholar metamaterials. Show less
Despite being the object of intense study, embryonic development has been difficult to model due to a number of reasons. First, complex tissues can be comprised of many cell types, of which we... Show moreDespite being the object of intense study, embryonic development has been difficult to model due to a number of reasons. First, complex tissues can be comprised of many cell types, of which we probably only know a subset. Therefore, we first focused on the discovery of cell types by single-cell RNA-sequencing (scRNA-seq). Cell types are routinely identified by clustering scRNA-seq data, however, there was no principled way to determine the right number of clusters. To improve cell type classification, we developed phiclust, a clusterability measure for scRNA-seq. Another challenge in a developing tissue is that many signaling processes and morphogenic events occur simultaneously, which makes it hard to isolate the individual contributions. For this purpose, I looked at stem cell derived in vitro systems, in which a small number of specific cell types can be combined deliberately and studied in isolation. My analysis of different model systems shows that cellular communication causes structural and transcriptional changes in the developing cells. Finally, while tissue organization has been characterized extensively, we lack generative models that can relate specific patterns to the underlying gene regulatory mechanisms. Therefore, I later focused on deep learning-based approaches to infer gene regulatory networks from observed spatial patterns. Show less
Single-molecule fluorescence was invented in the 1990s and has quickly developed into an indispensable technique in the biomedical sciences and condensed-matter research. It has revolutionized... Show moreSingle-molecule fluorescence was invented in the 1990s and has quickly developed into an indispensable technique in the biomedical sciences and condensed-matter research. It has revolutionized the fields of molecular biology, imaging (super-resolution), and catalysis, to name a few. In this thesis, we will apply fluorescence enhancement by single gold nanorods to extend single-molecule studies to chromophores with low fluorescence quantum yields and to high concentrations of probe molecules. Following single-molecule trajectories, we will explore variations in the electron-transfer rates of the metalloprotein azurin both from molecule to molecule and for the same molecule as a function of time. Evidence for conformational substates will be discussed based on dynamic heterogeneity. Show less
This thesis starts with an introduction to the quantum electrodynamical description of the interaction between light and matter. The role of optical cavities is discussed and the basic properties... Show moreThis thesis starts with an introduction to the quantum electrodynamical description of the interaction between light and matter. The role of optical cavities is discussed and the basic properties of rare-earth ions are reviewed. In Chapter 2 a bare ring resonator that is coupled to a waveguide is studied. Transmission spectra are measured, from which optical properties of the ring resonator and the waveguide are characterized. Chapter 3 addresses two technical issues that are essential for the research presented in this thesis: the implantation of rare-earth ions into the ring resonator and the permanent fiber connections to the waveguides. Chapter 4 is devoted to the research on the enhancement of the spontaneous emission rate in an ytterbium-doped ring resonator in the temperature range of 5.5-295 K as a result of the Purcell effect. Chapter 5 presents the results of measurements performed on an ytterbium-doped ring resonator in a dilution refrigerator in the range of 12 mK-4.7 K. In Chapter 6 collective effects of an ensemble of emitters in a cavity are theoretically studied with different initial states and pure dephasing rates by using the quantum Monte Carlo method. Chapter 7 concludes the thesis and presents an outlook for future work. Show less
Imaging subsurface structures with nanometer resolution has been a long-standing desire in science and industry. To obtain subsurface information one usually applies ultrasound, like e.g. in... Show moreImaging subsurface structures with nanometer resolution has been a long-standing desire in science and industry. To obtain subsurface information one usually applies ultrasound, like e.g. in echocardiography. Implementing ultrasound in an Atomic Force Microscope, a setup that is capable of imaging surfaces with atomic resolution, gives access to additional information. In particular, it is possible to image subsurface structures with nanometer resolution. However, it is not known why the subsurface structures become visible when applying ultrasound during the imaging with an Atomic Force Microscope. Based on a special excitation scheme, which makes use of two ultrasound excitations (one through the sample and one through the cantilever), Heterodyne Force Microscopy seems to be the most promising candidate for imaging deeply buried objects or structures with nanometer resolution. This thesis focuses on the poorly understood elements in Heterodyne Force Microscopy. We studied the ultrasound propagation in the sample, the dynamics of an ultrasonically excited cantilever near a sample that is also vibrating at a slightly diff erent frequency, and the generation of the heterodyne signal. The insight we gained in these matters allowed us to determine the contrast mechanism in a very well-de fined model sample, which contains gold nanoparticles buried in a soft polymer matrix. We show that the contrast in this system is determined by “friction at shaking nanoparticles”. Show less
This thesis presents a viable route towards the implementation of quantum computing utilizing quantum dots embedded in optical microcavities. Following the introduction of the big picture and long... Show moreThis thesis presents a viable route towards the implementation of quantum computing utilizing quantum dots embedded in optical microcavities. Following the introduction of the big picture and long-term visionary goal, general concepts fundamental to this field of research are described: quantum dots and microcavities, forming the physical system explored; and cavity quantum electrodynamics, the theoretical language used to describe their interaction. The physical structure and the optical mode composition in oxide-apertured micropillar cavities is analyzed. Permanent tuning methods achieving polarization degenerate cavities resonant with a quantum dot transition are illustrated. Active positioning of single quantum dots is developed providing an accuracy suitable to measure the interaction between a quantum dot and a cavity in the strong coupling limit. The possibility to waveguide-couple photonic crystal cavities on the same sample is explored. A theoretical description of the quantum-dot confined electron dynamics is presented. Presented are ideas how a hybrid quantum system could serve for implementation of a controlled NOT gate, and therewith be the building block for a quantum computer, exploiting the weak coupling regime. A Bell-state analyzer is the second scheme that is discussed. Results from reflection spectroscopy measurements on single quantum dots in a micropillar cavity are presented. Show less
The cell membrane acts as a barrier that controls the passage of substances from the outside to the inside of a cell. It is composed of various lipids organized in a bilayer with proteins embedded.... Show moreThe cell membrane acts as a barrier that controls the passage of substances from the outside to the inside of a cell. It is composed of various lipids organized in a bilayer with proteins embedded. Experimental data suggested that lipids are organized in nanometer-sized structures called membrane domains. I study the existence and the role of domains in living cells through single-molecule fluorescence microscopy. This technique allows pinpointing the position of each molecule with high spatial accuracy. I apply it to study the distribution of a membrane-anchored protein, HRas, in the inner leaflet of the membrane. From the single-molecule positions a map of protein distribution is reconstructed. Statistical analysis revealed dynamic partitioning in membrane domains. A different approach relies on tracking single proteins diffusion in the membrane. With this method I studied the influence of domains in the assembly of a two-component receptor, type I interferon receptor. I observed confinements of the components in small domains, which makes assembly faster and more efficient. Further, I present an advanced technique, to track proteins at microsecond time scale. After validating the technique on DNA, I applied it to GPI-anchor protein diffusion. These data confirmed the existence of theoretically proposed, complex diffusive modes. Show less
