P3: cGMP-dependent regulation of cell and tissue mechanics
Aims
To understand how cGMP signaling affects passive and active cell mechanics in healthy and disease conditions and how this connects to tissue mechanics.
Questions and Methods
cGMP and Vascular Biomechanics
- How do cGMP-related changes of the stiffness on a cellular level affect the mechanics on a tissue level (e.g. arteries, cancer)? Investigation of the stiffness of both VSMCs and the corresponding aortic tissue that they are extracted from (e.g. using AFM).
- Do mechanical properties of cells and tissues adapt to disease conditions (e.g. arterial stiffness, aneurysm, atherosclerosis) and can this be modulated beneficially with cGMP-related drugs?
- Does cGMP signaling affect the morphology and biomechanics of cells relevant to the cardiovascular system beyond platelets and VSMCs (e.g. fibroblasts)?
- Investigation of the effect of cGMP signaling on the active forces that cells (e.g. VSMCs, platelets, fibroblasts, neurons, cancer cells) exert on their environment using TFM. Do cGMP-related drugs alter mechanics during cell migration (e.g. platelets, cancer cells)?
Boston Internship
Seta Lab
In the Seta lab in Boston, the doctoral researchers will be trained in vascular biology. Specifically, they will learn about
- arterial stiffness,
- pulse wave velocity, and
- molecular biology of VSMCs.
Our conceptual hypothesis that cGMP signaling regulates biomechanics at a cellular level should give important insights into the various models of diseases within the consortium.
Boston Co-mentor
Assist. Prof. Francesca Seta, PhD
Link to Boston researcher lab
Doctoral Students
Daniel Lambton
Daniel Lambton earned his BSc in Nano-Science at the University of Tübingen. During his Bachelor thesis, he studied the motility of kinesin motors along the microtubule network with the goal of further understanding the transport complex for mitochondria. Following up on his Bachelor thesis, Daniel began the MSc in Nano-Science at the University of Tübingen, where he gained further interest in biophysics. In his Master thesis, he adapted an Atomic Force Microscope with a force sensor to characterise the viscoelastic properties of larger tissue samples. Now, he has begun his PhD in the laboratory of Prof. Dr. Tilman Schäffer where he continues to investigate the role of the cGMP signalling pathway in the mechanics of tissues.
Johanna Gabriela Rodriguez Cabezas (graduated in July 2023)
Johanna Rodríguez earned her BSc (Hons) in Pharmacology & Physiology at the University of Manchester (United Kingdom). During her bachelor thesis, she focused on the study of selective inhibitors of Tyrosine Phosphatases through docking and protein structural analysis. After her bachelor, she did an Erasmus Mundus Joint Master Degree in Nanomedicine for Drug Delivery with a specialization in “Production and Biotechnology applications of Nanomedicine”. She completed her first year of MSc at University Paris Descartes (France) and her second year at the University of Pavia (Italy). In her master’s thesis she studied the “Design, development, and characterisation in-vitro of theranostic nanobubbles for the treatment of pancreatic cancer” in the laboratory of Pharmaceutical Technology at the University of Turin (Italy). Recently, Johanna has joined the laboratory of Tilman Schäffer to do her doctoral studies. Here, her research focuses on cGMP signalling pathway, cardiovascular diseases, vascular biomechanics, and knockout mice in-vivo models.
Aylin Balmes
Aylin Balmes earned her BSc in Nano-Science at the University of Tübingen. During her bachelor thesis she studied the migration of blood platelets with phase contrast microscopy. After her bachelor she did the corresponding MSc in Nano-Science also at the University of Tübingen. With her elective courses she focused mostly on physics, especially biophysics. In her master thesis she studied the viscoelastic properties of cells with scanning ion conductance microscopy. On the side she is also pursuing a BSc in Physics. Aylin is now pursuing a PhD in the laboratory of Prof. Dr. Tilman Schäffer where she investigates the role of cGMP from a physics point of view.
Hendrik von Eysmondt (associated PhD student)
Hendrik von Eysmondt developed an interest in biophysics early in his B.Sc. of Biology at the RWTH Aachen, Germany, leading to a Bachelor thesis about the unidirectional growth of neuronal axons with microfluidics at the Institute of Biological Information Processing - Bioelectronics (IBI-3) at the Forschungszentrum Jülich.
He continued his studies in Aachen, obtaining his M.Sc. in Biology with a Master thesis in the adaptation of the sFIDA assay for an amyloidogenic protein in type 2 diabetes in his work at the Institute of Complex Systems 6 (ICS-6) at the Forschungszentrum Jülich.
Recently, he has joined the lab of Prof. Dr. Tilman Schäffer at the University of Tübingen to obtain his PhD, focusing on the mechanical properties of blood platelets, especially in the context of lipid interactions.
Konstantin Krutzke (associated PhD student)
Konstantin Krutzke gained his interdisciplinary knowledge in natural sciences during his BSc in Nano-Science at the University of Hamburg. For his bachelor thesis he investigated the removal of cytotoxic CTAB of gold nanorods for possible biological applications such as medical diagnostics or treatments. For his ongoing scientific career, he accomplished his MSc in Nano-Science at University of Hamburg in the field of micro-fluidics at the department of applied physics. He investigated the implementation of micro-fluidic, PDMS based nozzles for single particle imaging at the Hamburg based DESY as well as at research facility EuXFEL. For his doctoral studies Konstantin joined the lab of Prof. Dr. Tilman Schäffer at the University of Tübingen to investigate human thrombocyte volume changes with SICM in response to osmotic pressure.
Jan Seifert (associated Postdoc)
Jan Seifert studied physics at the University of Erlangen with focus on medical physics. For his diploma thesis he joined the lab of Prof. Tilman Schäffer and obtained knowledge about scanning probe microscopy in biological and medical applications. During his PhD he investigated shape changes and cytoskeletal dynamics in human platelets during activation with fast scanning ion conductance microscopy. As a postdoc, he gained interest in machine learning and currently focuses on the application of deep learning neural networks in optical platelet morphometry and the implementation of deep learning for measurement automation in scanning probe microscopy.
Key Publications
Seifert J, Rheinlaender J, von Eysmondt H, Schäffer TE. Mechanics of migrating platelets investigated with scanning ion conductance microscopy. Nanoscale 2022, 14:8192-9. doi:10.1039/D2NR01187E
Baumann J, Sachs L, Otto O, Schoen I, Nestler P, Zaninetti C, Kenny M, Kranz R, von Eysmondt H, Rodriguez J, Schäffer TE, Nagy Z, Greinacher A, Palankar R, Bender M. Reduced platelet forces underlie impaired hemostasis in mouse models of MYH9-related disease. Sci Adv 2022, 8:eabn2627. doi:10.1126/sciadv.abn2627
Nestele JA, Rohlfing A-K, Dicenta V, Bild A, Eißler D, Emschermann F, Kremser M, Krutzke K, Schäffer TE, Borst O, Levi M, Korin N, Gawaz MP. Characterization of GPVI- or GPVI-CD39-coated nanoparticles and their impact on in vitro thrombus formation. Int J Mol Sci 2022, 23:11. doi:10.3390/ijms23010011
Carlantoni C, Liekfeld L, Hemkemeyer SA, Schreier D, Saygi C, Kurelic K, Cardarelli S, Kalucka J, Schulte C, Beerens M, Mailer R, Schäffer TE, Naro F, Pellegrini M, Nikolaev VO, Renné T, Frye M. 2023. The phosphodiesterase 2A regulates lymphatic endothelial development via cGMP-mediated control of Notch signaling. Dev Cell (in press).