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Institute of Physiology and Pathophysiology

Nonlinear Microscopy

Figure 1: SHG signals from myofibrils change under rotation of the excitation laser polarization

Second Harmonic Generation

Second harmonic generation (or frequency doubling) is an effect that can be observed in certain nonlinear optical media, which emit radiation at a doubled frequency 2w when excited by an external electric field of the frequency w. The effect is well known for a number of crystals like quartz, but was also discovered for some biological structures like collagen or skeletal muscle myosin-II.


We are interested in the physical properties of second harmonic generation in these biological structures and applications for tissue imaging. The SHG signal intensity, for example, depends on the fiber orientation and the polarization of the incident light. Theoretical predictions for this dependency can be derived from standard equations considering crystal symmetries and then be tested with our experimental setup.

Figure 2: Two-photon excited fluorescence of Bodipy-Fl labeled actin in skeletal muscle

Multiphoton Fluorescence

Two or more photons of an infrared laser can be absorbed simultaneously by a fluorescent molecule to promote it to an excited state. The emission wavelength is the same as for standard single photon excitation.


As the effect of multi-photon excitation needs high energy densities, it occures mainly in the small center of the laser focus. Fluorescence is limited to this spot, which provides multi-photon microscopes with inherent high resolution. The main advantage over confocal microscopes is the higher resolution in deep tissue layers.


Recent Publications


Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5. FASEB J. 2017 Dec 5. pii: fj.201700384RR. doi: 10.1096/fj.201700384RR. [Epub ahead of print]


Modulation of glutathione peroxidase activity by age-dependent carbonylation in glomeruli of diabetic mice. J Diabetes Complications. 2017 Nov 22. pii: S1056-8727(17)31094-2. doi: 10.1016/j.jdiacomp.2017.11.007. [Epub ahead of print]


Sensitive mass spectrometric assay for determination of 15-deoxy-Δ12,14-prostaglandin J2 and its application in human plasma samples of patients with diabetes. Anal Bioanal Chem. 2017 Nov 16. doi: 10.1007/s00216-017-0748-1. [Epub ahead of print]


Role of protein carbonylation in diabetes. J Inherit Metab Dis. 2017 Nov 6. doi: 10.1007/s10545-017-0104-9. [Epub ahead of print]


AP-1 Oligodeoxynucleotides Reduce Aortic Elastolysis in a Murine Model of Marfan Syndrome. Mol Ther Nucleic Acids. 2017 Dec 15; 9: 69–79. Epub 2017 Sep 20. doi: 10.1016/j.omtn.2017.08.014


Allosteric inhibition of carnosinase (CN1) by inducing a conformational shift. J Enzyme Inhib Med Chem. 2017 Dec;32(1):1102-1110. doi: 10.1080/14756366.2017.1355793.


Transcription factor decoy technology: a therapeutic update. Biochem Pharmacol. 2017 Nov 15;144:29-34. doi: 10.1016/j.bcp.2017.06.122. Epub 2017 Jun 19. Review.


Local oxygen homeostasis during various neuronal network activity states in the mouse hippocampus. J Cereb Blood Flow Metab. 2017 Nov 3; 271678X17740091. doi: 10.1177/0271678X17740091


Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells. Stem Cell Res Ther. 2017 Oct 16;8(1):229. doi: 10.1186/s13287-017-0681-4.


Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory. EMBO J. 2017 Sep 15;36(18):2770-2789. doi: 10.15252/embj.201696369. Epub 2017 Aug 8

Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg


Phone:+49 6221 54-4056
Fax:+49 6221 54-6364