Most of what we know in Physics has been derived from experience with the inanimate world. One remaining challenge represents the transfer of these concepts to living objects such as cells, tissues, and entire organisms, where it is not certain if they are appropriate or even relevant. We investigate the mechanical and optical properties of living cells and tissues using novel photonic tools to test their relevance and importance for biological function. Our ultimate goal is the transfer of our findings to medical application in the fields of improved diagnosis of diseases and novel approaches in regenerative medicine with an impact on clinical practice.

The Optical Stretcher

The optical stretcher is a novel laser tool that can be used to trap and deform individual biological cells. The forces arise from the momentum transfer of light to the surface. The deformation can be used to study the cytoskeleton, which is an internal polymer gel resisting the external forces. Changes in the cytoskeleton are diagnostic for pathological changes and can be detected with the optical stretcher. Ultimately, we are developing a label-free, high-throughput cell analysis method for cancer diagnosis and stem cell sorting.

Schematic of an optical stretcher. In a flow chamber, cells in suspension can be trapped by two opposing laserbeams of low intensity, emanating from optical fibers. Increasing the intensity of the laserlight augments the forces at the surface of the cell, leading to measurable deformation. Publication: J.Guck et al., Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence Biophysical Journal 88:3689-3698 (2005)

Cells as Optical Fibers

Our discovery that Müller cells in the retina function like optical fibers made it on the PNAS cover. Publication: K. Franze, J. Grosche, S. N. Skatchkov, S. Schinkinger, C. Foja, D. Schild, O. Uckermann, K. Travis, A. Reichenbach, and J. Guck Müller cells are living optical fibers in the vertebrate retina Proc. Natl. Acad. Sci. U.S.A. 104(20):8287-8292 (2007)

Quite unlike smooth cylindrical optical glass fibers, most animal cells are irregular in shape and inhomogeneous in their optical properties. However, using a modified dual- beam laser trap, we found that individual Müller cells, which are elongated glial cells in the vertebrate retina, act as optical fibres. Confocal microscopy images of retinal tissue were consistent with this property also in situ. Specific geometrical and optical properties of Müller cells enable efficient collection and low-scattering transport of light through an otherwise scattering tissue. Their parallel array in the retina is reminiscent of fiber-optic plates used for low-distortion image transfer, thus suggesting a similar function in vertebrate vision. This assigns a new function to glial cells and solves a long-standing problem of the inverted retina.

Nerve Regeneration

The long standing paradigm that neurons in the CNS cannot regenerate is gone (after 3500 years). While most research to date is biochemical, there are also physical aspects that need to be considered. We are developing tools to investigate axonal growth and to stimulate and direct it in certain directions. Specifically, we are using IR laser beams to guide axonal growth into mechanical barriers, such as glial scars present after neurological trauma to see whether those pose mechanical barriers to nerve regeneration. We are also investigating the importance of mechanical cues for normal differentiation and axonal pathfinding during development.

Novel Imaging Tools

Schematic of the setup of a confocal microscope integrating a white light laser source. Taken from: T.Betz, J. Teipel, D. Koch, J. Guck, J. Käs, and H. Gießen Excitation beyond the monochromatic laser limit: Simultaneous 3-D confocal and multiphoton microscopy with a tapered fiber as white-light laser source J.Biomed. Opt. 10(5):054009 (2005)

We have successfully combined a white-light laser source with scanning confocal and multiphoton microscopy. This allows to work with any dye, rather than being limited by specific filter sets. This also opens the possibility for the development of novel imaging tools such as coherent-anti Raman spectroscopy (CARS) imaging or absorption microscopy in combination with 3D scanning. We are also interested in establishing quantitative imaging modalities of the mechanical properties of tissues. This includes ultrasound imaging of mechanical properties of tissue samples (glial scars, retinal layers) in vitro and NMR elastography of mechanical properties in vivo (brain, spinal cord).