Our laboratory aims to identify and further investigate the role of mechanical forces in cellular behavior and signaling, with the ultimate goal to improve human health and health care.

Our research has a central focus on cellular mechanobiology signaling in particular cell-matrix interactions that guide the control of gene expression and regulation. From our work there are two main clinically applied areas:

  • Applied Immuno-Mechanobiology: Mechanobiological signaling associated with lymphocyte activation and expansion.
  • Applied Neuro-Mechanobiology: Protein aggregation and phase transition in motor neuronal disease. The aim is to find molecular ways for intervention, and the development of next generation therapies.

In our interdisciplinary laboratory, besides cell culture we have a strong imaging core, which allows the development and application of multi-scale imaging techniques to quantify and characterize tissues, cells, single proteins, extracellular matrix, and cell-matrix interactions answer our mechanobiology research questions.

Our laboratory core techniques:

Biophysics: Single Molecule Localization Microscopy (STORM/PALM), high throughput SMLM, Structured Illumination Microscopy, STED, Lattice Light Sheet Microscopy, Airyscan, 2-Photon Microscopy, Traction Force Microscopy, single molecule FRET force sensors, MEMS devices, micro and nanostructuring, TOCCSL, FRAP, AFM

Biochemistry: surface coating, gene engineering, transduction, transfection, protein conjungation, ELISA, protein purification, gene expression, single cell transcriptomics, cell lines, immunological assays, GMP conform production, phenotyping and activation analysis, flow cytometry, FACS, DNA FISH.

Applied Immuno-Mechanobiology:

cellTogether with my research groups in Berlin and Zurich we investigate mechanobiological pathways and external cues that influence T cell and B cell signaling to tune their consequent functions. Here we explore how different conditions such as surface stiffness, topography, and hydrostatic pressure influence lymphocytes.

Are mechanical cues sufficient to trigger T cell activation? The contribution of mechanical cues to this process is not yet fully understood. How the structural modifications alter the transcriptional program of T cells at different stages, such as priming/activation, proliferation, effector functions, contraction, and long-term memory formation. Identifying and further understanding the genetic programme of mechanobiological-induced activation of T cells is one of our main research goals.

In our previous work, we have started to characterize both structural and functional aspects (functional genomics) of cell-surface interactions. We have shown the importance of traction forces that T cells apply via their actin rich microvilli and were further able to correlate forces with calcium signals as functional readout (Aramesh et al., Nanoletters 2021). In addition, our research continues investigating what is triggered cell signaling and functionality changes upon exposing T cells to nanoporous substrates enabled us via CD45 exclusion from activating microvilli to tune gene expression and significantly boost T cell activation (Aramesh et al., PNAS 2021).

In our laboratory we will continue to research on how specific mechanical cues can module immune cell function and furthermore explore their potential application to further improve immuno-therapeutic applications (Wagner and Klotzsch, Nature STTT 2022, Simsek and Klotzsch, BioEssays 2022).

To learn more about our applied clinical research project "immUni" CLICK HERE

Core Techniques:

Cell culture (primary and cell lines, BSL2) FACS CRISPR Confocal Microsccopy STORM nanoengineered surfaces

Applied Neuro-Mechanobiology:

cellOur laboratory is associated with a joint international research initiative, which aims to better understand protein aggregation and phase transition toward motor neuronal disease prevention, intervention, and the development of next generation therapies.

This collaborative project focus on the role of FUS protein, a DNA/RNA-binding protein known to be associated with transcription regulation, RNA splicing, transport, DNA repair and damage response. In neuronal cells, this protein plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis. Mutations of FUS are known to cause amyotrophic lateral sclerosis (ALS), a fatal adult motor neuron disease.

Together with a team of renown scientist (at ETH Zurich, Switzerland and MQU in Sydney, Australia), our group contributes to better understand FUS protein aggregation mechanisms by using live-cell and super-resolution microscopy combined with automated image processing.

Here we study FUS protein aggregation and the impact of large numbers of FUS variants on the subcellular distribution, nuclear re-localization and aggregate formation at a single cell and molecule level under the impact of altered stress conditions, such as mechanical forces and oxidative stress. Furthermore, we aim to address the impact of different mechanical forces on both the protein and cellular (neuronal) level. This research work will hopefully contribute to develop and establish novel imaging and sensor techniques applied specific FUS associated neuronal motor disease.

Core Techniques:

Super resolution microscopy FRET cell culture (primary, BSL2, neurons); bioinformatics proteomics

To learn more about our research projects