The Erlangen biophysics group studies the mechanical properties of cells, tissues and complex soft matter. In the case of cells, we study how they respond to their mechanical environment, how they interact with their extracellular matrix and with neighboring cells, and what mechanisms they employ for transmigration, invasion, adhesion, contraction, and cell division. To address these questions, our lab collaborates with other research groups worldwide to develop new technologies that draw from various fields, including soft matter physics, molecular cell biology, biochemistry, engineering, and applied mathematics.
Below we describe some of the ongoing projects and biophysical methods that we have implemented or developed. 
 
pingis observatoryHuddling in penguin colonies: We study the collective dynamics of penguin movements with image processing technologies adapted from cell migration and particle tracking. During the antarctic winter, emperor penguins have to sustain temperatures down to -50° Celsius combined with strong winds. To conserve energy, they move close together and share their body heat (huddling). Movements inside the huddle are highly coordinated so that every penguin gets to pass the warmest zone in the center of the huddle. We study how these huddles move, and how the penguins move inside the huddle, by taking time lapse images (every 1 sec) from an elevated position, and tracking the head of every single penguin for several hours. (link)
collagenshearMechanics of 3D-Collagen gels:  In collaboration with the rheology group of David. A. Weitz (DEAS, Harvard University) and the theoretical physics group of Fred MacKintosh (Vrije Universiteit Amsterdam) we investigate the mechanical properties of collagen gels on a macroscopic as well as a microscopic level. We measure bulk properties and determine the behavior of deformed collagen gels, i.g. by characterizing the deviations from an affine deformation of a bulk sample under shear (see video of a confocal section of collagen during shear deformation). (Münster et al. PNAS 2013)
gelporosityMorphology of 3-D collagen gels: Cell behavior in 3D collagen gels, such as migration speed, is strongly dependent on the collagen network morphology. By changing the protein concentration, polymerization temperature, pH, and crosslinker concentration, morphological properties such as pore size, fiber thickness, fiber length or branching ratio are changed. We quantify these properties of the collagen network by analyzing 3D confocal image stacks.The image shows a quantification of the gel porosity by computationally filling the fluid space with spheres of maximum size. This work is done in collaboration with Gerd Schroeder-Turk (Theoretical Physics group, Uni Erlangen) (Mickel et al. Biophys J 2008)
traction2DFourier Transform Traction Microscopy: This technique is used to measure the forces (tractions) that cells exert on their surroundings. These forces can be calculated from the deformation field of an elastic extracellular matrix (a polyacrylamide gel) in which fluorescent markers are embedded. (Butler et al. JAP 2002)
SEIsoProjection3-D Traction Microscopy: Under physiologic conditions in the organism, most cells live in a 3-D environment and not on a flat, smooth and hard 2-D plastic or glass surface. Traction forces in 3-D are important, for instance, for the migration of cells (such as cancer cells, or white blood cells) through the connective tissue. To measure forces, we extend ideas from 2-D traction microscopy (see above) to the third dimension. In analogy to 2-D traction microscopy, 3-D tractions can be calculated by measuring the 3-D deformation field of the connective tissue matrix surrounding a cell. The image shows the elastic strain energy stored in the extracellular matrix surrounding an invaded breast carcinoma cell. This work is done in collaboration with James P. Butler (Harvard School of Public Health). (Koch PlosOne 2012)
3dcellmigrationCell behavior in a 3-D extracellular matrix:  Cell behavior such as force generation, migratory behavior, cell adhesion, focal adhesion formation, cytoskeletal organization and dynamics of cells in 2-D culture systems has been shown to substantially differ from those observed in a 3-D environment where cells are embedded in a flexible, degradable 3-D extracellular matrix. We use reconstituted collagen fiber networks to study cells in a more physiological 3-D environment.

VinculinActinVinculin in cellular mechanotransduction: Vinculin is a protein responsible for the dynamic coordination and regulation of the focal adhesion complex (FAC) formation and the mechanical properties in cells. We have performed extensive studies in model cell systems in the presence and absence of vinculin and explored the relationship between cell stiffness, contractile forces and mechano-chemical signaling. The image shows vinculin (stained in green) and the actin cytoskeleton (red) of a fibroblast. (Mierke JBC 2010) (Diez BBRC 2011) (Thievessen et al. J Cell Biol 2013)

FAKp130Cas-Vinculin interaction is critical for mechano-transduction and cell signaling. p130Cas is a focal adhesion protein that acts as a primary mechanical sensor in cells. Its binding to vinculin is important for mechano-transduction and initiates the activation of downstream pathways such as the extracellular signal-regulated kinase (ERK1/2) pathway. Phosphorylation of p130Cas on tyrosine residue Y12 or the mutation of this residue to a phospho-mimicking glutamate prevents vinculin binding, reduces the localization of p130Cas to focal adhesion sites, and suppresses ERK1/2 signaling in response to mechanical stress (Janoŝtiak et al., CMLS, 2014; Goldmann, CBI, 2014).

Focal Adhesion Kinase

Focal Adhesion Kinase and cell mechanics. Focal adhesion kinase (FAK) is a central signaling and scaffolding protein of the focal adhesion complex. It is believed that FAK plays a central role in mechanotransduction and affects focal adhesion dynamics. We aim to determine the influence of FAK on cellular mechanics using biophysical approaches. (Klemm et al. BBRC 2010) (Fabry et al. Biophys J2011) (Lange et al. BBRC2013)

Plectin

Biomechanical characterization to understand the pathogenesis of myofibrillar myopathies.Intermediate filament (IF)-based cytolinker proteins affect cells mechanically by interlinking and anchoring cytoskeletal filaments and act as scaffolding and docking platform for signaling proteins to control cytoskeleton dynamics. We plan to compare the biomechanical properties, morphological changes, and intrinsic mechanical stress response changes in immortalized desmin and filaminC-deficient mouse/human myotubes using the cell stretcher, magnetic tweezer, and traction microscope. In what way cellular signaling as well as cytoskeletal restructuring and reorganization processes are involved will be elucidated (Bonakdar et al., BBRC, 2012; Winter et al., JCI, 2014).

 
tweezeranimationMagnetic Tweezers: Magnetic micromanipulation using Magnetic Tweezers is a versatile biophysical technique and has been used for single-molecule unfolding, rheology measurements, and studies of force-regulated processes in living cells. We developed a magnetic tweezers setup for the application of precisely controlled forces up to 100 nN onto 5 micrometer magnetic beads. High precision of the force is achieved by a parametric force calibration method together with a real-time control of the magnetic tweezer position and current. High forces are achieved by bead-magnet distances of only a few micrometers. Applying such high forces can be used to characterize the local viscoelasticity of soft materials in the nonlinear regime, or to study force-regulated processes and mechano-chemical signal transduction in living cells. (Kollmannsberg et al. RSI 2007)
NanoscaleParticleTrackingNanoscale Particle Tracking: Ligand-coated beads can also serve as fiducial markers of whatever (specific) receptor and cortical or cytoskeletal components they are bound to; the bead motion then reports the remodeling of these components. The movement of the beads (or any other particle visible with phase contrast, modulation contrast or fluorescence microscopy) can then be tracked with nanometer resolution. (Raupach et al. PRE 2007)
dynFibNet1 Models of cell migration: We are developing models that quantitatively describe cell migration as a stochastic process. For this purpose, we apply analytical tools from statistical physics, the theory of nonlinear complex systems and computer simulation methods. According to the multi-scale nature of biological cell migration, we investigate the problem on different levels, ranging from the underlying molecular processes up to the mesoscopic behavior of living cells:

(1) Biochemical reaction networks: Can reaction networks be treated as boolean logic networks, or do intrinsic fluctuations and their modulation by external signals play an active role in biology?
(2) Acto-myosin cytoskeleton: What is the source and function of the universal long-time correlations found in the spatial fluctuations of the cytoskeleton? (Metzner et al. PRE 2007)
(3) Motion of individual cells within complex material: Which strategies do cells apply in order to move through a dense biopolymer network?
(4) Collective cell migration: Do cancer cells cooperate when they invade into new tissue and try to form secondary tumors? (Lange Exp Cell Res 2013)