In detail, we are interested in answering the following fundamental questions:
How can cells control and tune their mechanical properties?
How do cells mechanically interact in development, immune response and cancer progression?
What intracellular forces and mechanical changes happen during cell migration and cytokinesis?
What new statistical mechanics models can explain cytoskeletal mechanics and organization?
To answer these questions we aim at a detailed physical description of the mechanical processes that are used by living cells. For this we continuously develop new measurement techniques such as optical tweezers, high accuracy particle tracking, traction force microscopy, micropipette aspiration and UV laser ablation.
The current projects of the lab
Dynamics of cellular blebs in M2 cells. The membrane (green) expands due to hydrostatic pressure generated by the acto-myosin cortex (red).
Intracellular passive and active microrheology in dividing epithelial cells
Visualized actin (green) and nucleus (red) of dividing MDCK cell.
We are interested in the underlying mechanism of organelle distribution during cell division. While there is a good understanding of chromosome segregation during cell division, the distribution of different organelles remains poorly understood. A systematic transport is not known for symmetrically dividing cells. It is assumed that the distribution of organelles relies on passive diffusion and stochastic transport. If this is sufficient to mix larger organelles with low copy number, especially in highly polarized cells, is not clear. A possible mechanism to enhance distribution throughout the cell is the increase of random mobility. This could be achieved by active, undirected fluctuations, e.g. generated through motor protein activity. To address the question if this is true, we use optical tweezer based passive and active microrheology measurements on exogenous particles inside dividing epithelial cells. The results are used to calculate intracellular viscoelasticity and mechanical activity to pinpoint the influence of active cytosolic mixing during cell division.
Collective cell migration in development
Early zebrafish development.
Collective cell migration is a fundamental process during embryogenesis and its initial occurrence, called epiboly, is an excellent in vivo model to study the physical processes involved in collective cell movements that are key to understanding organ formation, cancer invasion, and wound healing. In zebrafish, epiboly starts with a cluster of cells at one pole of the spherical embryo. These cells are actively spreading in a continuous movement toward its other pole until they fully cover the yolk.
We want to understand how this collective movement is organized from a physical point of view. What are the force generating mechanisms? Can we reconstruct the collective behavior applying rather simple physical models? In order to answer these questions we use advanced imaging techniques as e.g. light sheet microscopy, analyze the data by tracking cells in the acquired images and perform viscoelastic measurements using optical tweezers.
Collective cancer cell migration
CT26 cancer cells (green) invading a collage I matrix (red).
Collective migration is a gold standard behavior that has been commonly observed during morphogenesis and during wound healing. Cancer cells move collectively in order to migrate and overcome the space constriction due to densely growing cells at the center. This is characterized by cell-cell adhesion differences, the extracellular matrix or cell-substrate interactions, and the intercellular cross-talks in-order to metastasize. The mechanisms and the physics behind the coordinated behavior of cells have been studied recently at the 2D level, and in-vivo tissue homeostasis. However due to the challenges involved in reproducing and imaging tumor spheroids; collective motion of 3D cancer invasion is not yet completely understood. With the use of Light Sheet Microscopy, we have been able to consistently image HeLa spheroids for long hours (~48h) at sub-cellular resolution. This has enabled us to look deeper into how the velocity of cells correlate with one another, via particle tracking over a period of time, as they radially arrange themselves in collagen.
“Forcing” changes in the adult stem cell transcriptome
Ex vivo contracting muscle tissue.
Skeletal muscle is the most widespread tissue in the human body and supports essential functions e.g. breathing, swallowing and movement. Upon injury, muscle stem cells, also known as satellite cells (SCs), are activated and eventually regenerate muscle tissue by fusion of differentiated myogenic progenitor cells to form new myofibres. Disorders during this myogenic program may lead to severe muscular dystrophies.Whereas many signal transduction pathways are known to be responsible for SC fate decision, especially mechanical niche cues are far less understood. Therefore, we are tremendously interested in a variety of forces, which are exerted on SCs in muscle tissue and are responsible to wake SCs up from their quiescent state to exhibit all their great regenerative potential.