The traditional way of addressing questions related to the function of the brain is by studying the nervous system of various organism. Due to the complexity of these systems, it is very difficult to address fundamental questions. This leads to a lack of consensus even on seemingly basic questions such as “what is information” and “how is information stored and processed” in the brain. A new, ...
Nanopore sensors quantify protein levels but face challenges in live cell detection, such as portability, precise pore size control, and improved specificity. We aim to advance nanopore microscopy for single-cell profiling and explore its potential in cell biology. This presentation introduces interface nanopores as microscopic windows for real-time cellular process analysis, like protein...
The DNA origami is an excellent breadboard to accommodate and manipulate nanoparticles and small molecules with a nanometer precision. Just recently, an orientation of covalently bound molecules has been realized through stretching the fluorophores incorporated into DNA origami structures.
Here, we utilize this method to produce highly efficient plasmonic system. Investigated photonic...
In my PhD project, we pioneer a novel passive sensor concept that leverages the tunable properties of acoustic metamaterials for medical implants, unlocking the potential of acoustic metamaterials in the biomedical domain. Specifically, we have developed an implantable high-resolution temperature sensor that reaches the mK level. Such resolution enables ultrasound detection of thermal...
The Swiss Light Source at PSI is undergoing an upgrade to a so-called diffraction-limited storage ring (DLSR), promising a reduction in beam emittance (the product of the electron-beam divergence and cross-section) from 5500 pm.rad to 157 pm.rad. The brilliance of ‘SLS 2.0’ will increase at some beamlines by well over 1000, thanks also to novel undulator and optics technologies.
This heralds...
We study water state in lipidic mesophase. First, we investigated water in an unfrozen lamellar phase (La). Through the combination of differential scanning calorimetry and dielectric spectroscopy, we understood the crystallization and the dynamics of water in L. At a lower hydration, the nanoconfined water remains in liquid down to -120 °C. In addition, the phase structure of lipidic...
The cryoWriter is a robot for cryoEM sample preparation. It transfers samples with microcapillaries on grids and vitrifies them. The system can handle globular, membrane, or filamentous proteins, as well as small cells.
The whole procedure takes less than 2 minutes per grid, of which the integrated glow discharge takes up most of this time. A high level of control results in repeatedly...
Recent study has reignited interest in the physiological implications of protein interaction with intracellular small molecules, particularly their weak non-specific interaction believed to influence many protein properties. Here, we take ubiquitin as a model to examine in depth by NMR its interaction with proline, an amino acid present prevalently in cellular environment. Our findings show...
The development and research on metamaterials opens the doors for futuristic technologies using their custom-designed properties to interact with and manipulate the flow of light.
The effectiveness of such materials depends vastly on the size of
the interactive material and research is driving into the direction of fabricating larger connected and homogeneous surfaces of metamaterials....
Per- and polyfluoroalkyl substances (PFAS) are employed extensively for their amphiphobic properties, but are being banned for environmental and health reasons. No competitive alternatives exist; one key reason is that oleophobicity is not well understood.
Here, the surface force apparatus (SFA) is used to explore physical and interfacial properties of a promising substitute:...
The helical periodicity and layered structure in cholesteric liquid crystals (CLCs) may be tuned to generate structural color according to the Bragg's law of diffraction. Here, the possibility of using amyloid CLCs is reported to prepare films with iridescent color reflection and opposite handedness. Right-handed CLCs assembled by left-handed amyloid fibrils are dried into layered structures...
AFM-IR, or photothermal infrared nanospectroscopy, combines atomic force microscopy (AFM) and infrared (IR) spectroscopy, enabling chemical analysis with a spatial resolution in the order of 10 nm. Tapping mode AFM-IR is well-suited for the analysis of soft matter systems such as nanoparticles, biological macromolecules and polymers. The method allows mapping of the samples at specific...
Musculoskeletal tissues develop under the influence of dynamic mechanical loading regimes, which is reflected in the highly anisotropic organization of the tissues. In order to engineer tissue such as cartilage, tendon and muscle for use in regenerative medicine, my laboratory uses architected hydrogel scaffolds to provide relevant cell-instructive cues. Our approaches are based either on...
The identification of ligands to biologically relevant targets is a central aspect of pharmaceutical research. Traditional methods such as high-throughput screening probe individual compounds in single reaction vessels for biological function and are typically limited to max. 10^6 compounds. In contrast, DNA-encoded chemical libraries are pooled collections of >10^9 compounds and allow for...
Focal Molography (FM) is an emerging label-free method for real-time molecular interaction analysis in complex environments. This contribution will cover the basic physics of FM and explain its advantages over established techniques due to its operating principles. We will then explore the application of FM for rapid and multiplexed kinetic characterization of small molecule hits from...
Interactions between mucosal secretory IgA (sIgA) and bacterial surface glycan (O-antigen) protect against Salmonella Typhimurium (S. Tm) infection. sIgA binding induces "enchained growth," reducing the number of single bacteria and enhancing enchained pathogen clearance in fecal stream. Half-life of long bacterial chains depends on detailed force-dependent kinetics of sIgA–O-antigen...
Integral membrane proteins are drug targets for the majority of all approved drugs. Structure-based drug discovery on soluble proteins is managed well within the project timelines and portfolio changes in pharmaceutical industry, but transmembrane proteins are still underexplored because of their challenges to be expressed, purified and get high resolution structures or enable biophysical...
The cytoskeleton and molecular motors play a critical role in the spatial and functional organization of living cells. However, the corresponding molecular interactions are often not directly observable in vivo. Here, we use two examples to discuss how biophysical models can help inferring biological mechanisms from experimental observations. The first example in budding yeast demonstrates how...
Existing approaches in directed evolution are suited for evolving steady-state properties such as enzymatic activity or protein binding. A fundamental problem remains how to evolve dynamic proteins. As a solution, we present coupling such proteins to a dynamic system essential for cell survival. We first evolved mutants of a LOV transcription factor that were stronger, less leaky, or...
Living organisms rely on flows to perform essential functions that range from swimming and feeding in unicellular organisms to mucus clearance in humans. These flows are generated by the integrated activity of thousands of micrometer scale active filaments, known as cilia. Collections of cilia exhibit highly stereotypical temporal patterns, namely metachronal waves. While temporal patterns of...
Tissue physical states and rigidity transitions are known to be controlled by various cellular properties but the impact of sub-cellular organelles on tissue states remains unexplored. By combining theoretical modeling with in-vivo experiments, we uncover a novel nuclear jamming transition. Introducing nuclei as soft particles in the model, we investigate how nuclei affect tissue states....
Biological cellular tissues often exhibit domains of orientational order, separated by topological defects where order vanishes. Those regions concentrate active stresses generated by cell force dipoles and give rise to spontaneous flows.
We use an agent-based model to describe cells as multi-particle filaments and incorporate mechanical activity in terms of individual cell force dipoles....
The dynamic mitochondrial network functions as the cellular energetic and signaling hub. Its essential multi-copy genome is packaged in nucleoids, regularly distributed along the mitochondrion, and surrounded by an intricate inner membrane that restricts movement. Each nucleoid’s integrity affects local mitochondrial fitness, and dysfunctional regions are peripherally ejected for...
Transcription factors (TFs) organize within the nucleus in clusters. These clusters play a crucial role in regulating transcription activity. In zebrafish, two large Nanog clusters form soon after fertilization. Nanog proteins possess a DNA-binding-domain, for proper condensate assembly, alongside with two disordered domains, facilitating protein-protein interactions. However, the...
Fluorescence microscopy stands as an indispensable tool in biology, offering unparalleled specificity and resolution. However, every advanced experiment is limited by phototoxicity and photobleaching. To address this limitation, we integrate phase-contrast imaging for event detection in an adaptive acquisition that uses fluorescence only during events of interest. This requires detecting...
Single molecule localization techniques offer a direct measurement of the position of individual molecules, which can be computationally combined to reconstruct objects of interest. On the other hand, the Single-Pixel Imaging (SPI) concept allows to capture an image using just a single photodetector. Remarkably, in both techniques, a geometric description of the sample is typically obtained...
Self-organization in biological systems is crucial for coordinating vital functions. One such example is the collective motion of slender cellular appendages called cilia. In dense arrays, neighboring cilia beat with a phase shift, forming metachronal waves essential for large-scale flow generation. Despite their prevalence, the mechanisms governing cilia patterns and their connection to flow...
Cilia are hair-like organelles on the surface of many cells beating collectively in a metachronal wave pattern creating essential fluid flows. The mechanisms behind cilia coordination remain poorly understood. We use Paramecium, a unicellular organism containing a few thousand cilia to study how metachronal waves emerge. By quantifying the cilia density, characterizing networks connecting...
Having the correct number of centrioles is crucial for the cell and this is ensured by duplicating centrioles strictly once every cell cycle. While three important proteins have been identified, the mechanism by which these provide incredibly robust control of organelle copy number remains unknown. I will discuss Turing-based theoretical approaches to understand how self-organization and...
Symmetry breaking in living systems is a fundamental process for building complexity across different scales. In Caenorhabditis elegans, symmetry breaking in the one-cell stage embryo results in anterior-posterior polarization defined by the PAR proteins. The actomyosin cortex is a key component in this process, where a local relaxation in actomyosin contractility triggers cortical flows...
Respiratory chain super-complexes (SC) are naturally occurring assemblies of oxidative phosphorylation protein complexes. Their role in facilitating mitochondrial ATP production remains debated. While altered metabolic conditions affect SC occurrence and isolated SC have been structurally characterized, their spatial organization and stoichiometry within mitochondria remain unclear. In this...
Protein based supramolecular assemblies have been shown to play an important functional role in many biological processes.
Some proteins that undergo phase separation have been extensively characterized, helping us understand the general principles of this process. However, we have limited information on which portion of the proteome can undergo phase transitions, especially under...
When double-strand breaks happens to the DNA, the cell arrests at the DNA damage checkpoint, preventing its entry into mitosis until the breaks are eventually repaired and the cell can proceed to mitosis. If the breaks persist, cells may bypass the checkpoint, this is called override. It is known that the override time depends on the number of breaks, but how the cell measure this number isn’t...
When faced with chromosomal double-strand DNA breaks, cells activate a complex DNA Damage Checkpoint response that arrests the cell cycle and reprograms gene expression. Although the regulators of the core network have been intensively explored, the mechanism of checkpoint override remains poorly understood. To address this gap, we developed novel strategies to shed light on how the DNA Damage...
Despite being used for decades as stabilizers, amino acids (AAs) remain mysterious components of many medical and biological formulations. In this talk, I show that AAs have a general ability to stabilize weakly interacting proteins in solution. By precicely measuring the second osmotic virial coefficient we demonstrate that AAs are able to modulate protein interactions at mM concentrations....
Small-molecules like amino acids have been known to be stabilizers for proteins for decades yet their working mechanism remains disputed. We demonstrate a direct interaction description, potential of mean force (PMF), of such phenomenon in both non-biological colloids and protein dispersions. Our results suggest this effect to be of fundamental colloidal nature as opposed to a protein specific...
Cell metabolism is the engine that fuels all living processes. Recent experimental results highlight that it dynamically self-organises in space, including via phase separation. We use minimal theoretical models to study the energetics and spatial organisation of cell metabolism, with a focus on glycolysis. Specifically, we discuss efficiency and power of this metabolic engine and motivate why...
A population composed only of drug-sensitive bacteria cannot survive the addition of a biostatic drug at a sufficiently high concentration and for sufficiently long. However, if at least one resistant bacterium is present before drug addition, it can lead to population rescue through resistance. How does spatial structure impact the survival of a bacterial population upon biostatic drug...
Mitochondria orchestrate vital cellular processes such as metabolism, signaling, and apoptosis, all of which depend on the dynamics and connectivity of the mitochondrial network. Disruptions by fragmentation or hyper-fusion of the networks are observed in dysfunctional cells and in various neurodegenerative disorders.
Branching patterns within mitochondrial networks can emerge from membrane...
Homotypic mitochondrial contact sites are rare and some exhibit a regular lattice-like bridging pattern between neighboring mitochondria, called intermitochondrial junctions (IMJs). In human T cells IMJs occur in a subpopulation of cells but their function, protein identity and structure remain unknown. T cell activation and memory cell formation is controlled by mitochondrial activity and...
Membrane potential is a ubiquitous cellular feature, fundamental for intercellular signaling of excitable cells, and also critical for intracellular communication. The mitochondrial membrane potential in particular offers a readout of organelle function. Interestingly, mitochondria can form electrically coupled networks, undergoing spontaneous and synchronous transitions in membrane potential....
