Some of my research projects are explained below. You can also have a look at my publications and at my current group's webpage.
Animal models are widely used in cancer research to test drug or dosage. In vitro models are an alternative to those. However, 2D cell cultures are not sufficient, because they do not recapitulate the tumor microenvironment. We are therefore developing 3D cancer models that mimic the most significant aspect of tumors and their microenvironment, to be able to use them for future drug testing platforms. We are focusing on skin squamous cell carcinoma. We use hydrogels with defined biophysical and biochemical properties that mimic the skin architecture and allow for tumor growth and invasion.
Funding: SNSF (NRP79)
Related Publications:
Protein isolation from 3D scaffolds. Current Protocols, 4, e966.
We are using granular hydrogels developed by the Macromolecular Engineering Lab to enable immunomodulation (increasing or decreasing inflammatory signals) in the context of a chronic wound. The biomaterial is made of granular hydrogels jammed together, and is capable of acting as a bioactive sponge, soaking up biomolecules.
Funding: Helmut Horten Stiftung, ETHZ
Mechanical memory is a phenomenon of loss of cell plasticity due to prolonged mechanical stress. It has been observed first on stem cells and fibroblasts cultured for multiple passages on stiff substrates. The phenotype that cells acquired on stiff substrates are maintained after passage to softer substrates. We are now investigating how 3D hydrogels lead to memory or phenotypic bias of the initial cell population
Relevant publications:
Implications of cellular mechanical memory in bioengineering, ACS Biomaterials Science & Engineering, 9, 11, 5985–5998 (2023)
We are developing 3D models of skin tissue, focusing on the dermal layer. For this, we use different types of hydrogels, in which we encapsulate fibroblasts sparsely. We then subject these 3D systems to mechanical stresses (hydrostatic pressure, osmotic pressure) to determine what the cellular stress response is.
We also develop specific disease models, e.g., a model of fibrosis in which stiffening of the tissue causes dysfunction.
Funding: SNSF, ETHZ
Related Publications:
Protein isolation from 3D scaffolds. Current Protocols, 4, e966 (2024)
Serine protease 35 regulates the fibroblast matrisome in response to hyperosmotic stress. Science Advances, 9(35), eadh9219. (2023)
Control of hydrostatic pressure and osmotic stress in 3D cell culture for mechanobiological studies, Biomaterials Advances 145, 213241 (2023)
We are developing hydrogels for 3D culture with defined physical, mechanical and biochemical properties. These properties include controlled stiffness, porosity (nanoporosity, macroporosity), stress relaxation, adhesive propertiesm and cell confinement. We also are making some of these tunable by light to enable spatio-temporal patterning of hydrogel properties.
Funding: ETHZ
I studied the sensitivity of mouse embryonic stem cells to stiffness and adhesion cues, and other mechanical stresses. To do this, we often grew the embryonic stem cells on hydrogels that were soft or stiff. These hydrogels had a thin layer of matrix protein on their surface to which cells could attach. But because this layer was not uniform and equal on soft and stiff hydrogels, we first developed a new attachment procedure for protein, that ensured strong tethering of proteins to the gels. This technique was called StemBond hydrogels. We used them to demonstrate that soft hydrogels help maintain the properties of pluripotent stem cells (self-renewal and pluripotent differentiation capacity) through mechanosensitive ERK signaling.
Related Publications:
StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells. Nat Commun.12, 6132 (2021)
Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate, Cell Stem Cell 28 (2) 273-284.e6 (2021)
Abscission couples cell division to embryonic stem cell fate, Dev. Cell 55 (2) 195-208.e5 (2020)
Nuclear mechanotransduction in stem cells, Curr. Op. Cell Biol. 64, 97-104 (2020)
In my PhD project, I used micropatterned substrates and traction force microscopy to investigate how cell shape and cell tension were related. Cell shape was defined by the radius of thick cables of actin and myosin at the cell edge. Cell tension is both the surface tension (tendency to minimize cell area) and line tension in the stress fibers (tendency to straighten the cell edge). Myosin contractility contributes to both. By inhibiting myosin contractility and measuring the subsequent changes in shape and traction forces, the contribution of elastic tension and myosin activity could be determined. The line tension was modeled with a minimal viscoelastic model, containing an elastic term and an active term representing myosin activity. Surface tension is dominated by myosin activity.
Related publications:
Cell shape dynamics reveal balance of elasticity and contractility in peripheral arcs. Biophys. J. 108 (10), 2437-2447 (2015)
An actin length threshold regulates adhesion maturation at the lamellipodium/lamellum interface. Integr. Biol. 5(6), 865-876 (2013)
Microsurgery-aided in-situ force probing reveals extensibility and viscoelastic properties of individual stress fibers. Sci. Rep. 6, 23722 (2016)