Microsystems & Biophysics of Tissues

Dr. Claus Fütterer

Publications

Selected Publications

DEVELOPMENTAL BIOPHYSICS

Development is an integrated process based on numerous biochemical but also physical properties. The physics of regeneration and development has been introduced again after more than 100 years of predominating molecular research in 2003 at the Institut Curie (Fuetterer et al Eurphys Lett 2003). Especially mechanical properties (forces) and the related self-organization have been neglected until recently when it could be shown that mechanical compression can even influence the expression of cancer and development genes under certain conditions (Whitehead et al. EMBO Journal 2006). The feed-back loop is closed: Mechanics-> Genes -> Proteins -> Mechanics. The logic conclusion is that neither genes nor mechanics are controlling the dynamics but both in an equivalent manner. Our goal is to study this feed-back mechanisms with emphasis on the mechanical side.


Movie of zebrafish development.

TISSUE-MECHANICS

Biophysics of Regeneration with Hydra vulgaris

Hydra Vulgaris, a simple, 1cm long fresh water polyp exhibits versatile reproduction and regeneration capabilities: lost body parts are replaced, even more strikingly, a disorganized cluster of a few thousand Hydra-cells may regenerate to an animal under appropriate conditions. During this process of regeneration, Hydra first builds a hollow sphere consisting of a cell bilayer. This cell ball undergoes subsequent shape transformations, at a later stage it creates tentacles and a foot to form an animal. We describe and analyze the transformation of the hollow sphere to the first non-spherical shape by means of contour analysis. Using a new contour retrieval algorithm we observe that the cell ball shows characteristic oscillations in size and shape which accompany symmetry-breaking. Quantitative analysis of these oscillations provide information on the cell-bilayer mechanics and hydrodynamic flows involved. In order to explain the origin of the observed oscillations, we propose three different physical scenarios of oscillation generation. Why studying a species so far from human species? It seems so that development follows the same physical and partially even biochemical principles. Cells have to know to which differentiation and at what time they have to bifurcate. Self-organization is one of the major key elements. Our hypothesis is that the required signaling is partially mechanical and also biochemical with emphasis onto the first aspect (without ignoring the second, of course!). Tissues like skin, indestines or Retina act and react mechanically. Pseudo-periodic oscillations are often observed during rearrangements or morphogenetic processes of the tissue. How are the observed oscillations linked to gene expression and post-translational modifications?


Selforganized folding of Hydra Vulgaris toroids leads to complete regeneration of the organism.

NEURONS

The aim is to study neurons and neuronal axons in a given micro-patterned way and to measure signaling paths.


Separation of soma and distal axons by microchannels. Collaboration with University of Paris.

DYNAMICS OF SUPERPARAMAGNETIC PARTICLES

We also study the dynamics of superparamagnetic micro- and nanoparticles. Brownian motion (temperature dependent), hydrodynamic friction and magnetic forces lead to a surprizingly complex dynamics, which we are investigating currently. We also investigate new applications in biomedical research.


Customized microfluidics microscope.

CANCER

The majority of human colorectal cancers result from Wnt-activating mutations in the APC gene (guardian), but the progression from initial mutation through adenoma to carcinoma and metastasis nonetheless requires unknown environmental signals to further increase levels of nuclear beta-catenin. The finding that an oncogenic transcriptional program can be induced by mechanical stimulation via nuclear translocation of beta-catenin in a genetically susceptible host reveals that the precision mechanical microenvironment is a potential contributor to tumourigenesis. We test the ability of colon explants from normal or APC deficient mice to respond to physical strain by analysing changes in the distribution of beta-catenin and expression of its target oncogenes. Therefore, unprecedented new systems to control the mechanical micro-environment properly have been developed.

CELL SYMMETRY IN MICROSYSTEMS

Cell adhesion, polarisation and migration are strongly related to cancer. Here the scope is on the organisation of the cyto-squeleton of cells immobilized on different symmetric and asymmetric micro-patterns. Microfluidics allows a precise perfusion with well defined and short (on a reaction scale of the cell) pulse of stimulants or chemokines. Further if is feasible to expose only parts of the cell to gradients opening the door to completely new experiments to study cell-signaling. This allows to investigate the reaction of the cytoskeleton on asymetrically microstructured fluidic environment for the sake of understanding the relation between the actin and microtubule network, the centrosome and the focal adhesion points. In addition an ongoing project is to grow actin and mircotubule networks in microchannels in order to investigate their mechanical and biochemical relation and the nonlinear spatio-temporal dynamics for the force generation and migration control of the cellular force generators.

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