Research / Methods

•  Magnetic Manipulation of Cellular Functions / Development of Magnetogenetics

Many cell functions rely on the coordinated activity of signalling pathways at a subcellular scale. However, there are few tools capable of probing and perturbing signalling networks with a spatial resolution matching the dimensions of their activity pattern. In our group we develop a generic magnetic manipulation approach - refered to as "Magnetogenetics" - where functionalized magnetic nanoparticles are manipulated with external magnetic fields. The nanoparticles exhibit proteins which are responsible to trigger a particular signaling pathway and act as nanoscopic signaling hubs. Via this active and remote manipulation of the signaling proteins we aim to decipher the spatio-temporal pattern needed to trigger a specific signal inside a cell. 

Novoselova, Neusch et al. Nanomaterials (2021) accepted 

Toraille et al. Nano Letters (2018), 18, 7635-41 https://pubs.acs.org/doi/10.1021/acs.nanolett.8b03222

Lisse, Monzel et al. Advanced Materials (2017), 29, 1700189https://doi.org/10.1002/adma.201700189; 

Monzel et al. Chemical Science (2017), 8, 7330-8,https://doi.org/10.1039/C7SC01462G; (review)

 

• Biomimetic / Synthetic Membranes

Biological membranes are one of the most fascinating hallmarks of life. To enable cellular life, membranes must be able to reconcile a dazzling array of partly contradictory demands: on the one hand, membranes form the spatial boundary of life separating the intracellular from the external environment and hence must be mechanically stable enough to withstand pressure and tension changes in their environment. On the other hand, membranes must be sufficiently malleable to allow cell growth, cell division, or dynamic changes of cell shape. When cells form a tissue, the cells connect to each other in a process called adhesion which exerts mechanical stress or tension on the membrane. In addition, membranes must allow for the flow of information and the passage of nutrients into the cell, which is typically realized by accumulatin membrane molecules into characteristic domains. The establishment of such heterogenous molecular distribution in the membrane may be pictured as the formation of characteristic phases. 

Biomimetic membranes, such as giant unilamellar vesicles (GUVs) or supported lipid bilayers (SLBs), are excellent model systems to study the physical aspects of these biomembrane functions. As artifical systems the membrane can be composed from a well known mixture of particular molecules (just like a system of LEGO bricks from which a structure is built). For example, the membranes can be designed to exhibit particular molecules which mediate biomembrane adhesion and to probe the strength and kinetics of bond formation. They can also be designed to organize into phase separated membrane regions to study how characteristic membrane regions such as signaling domains form.       

Kleusch et al. Int J. Mol. Sci. (2020), 21, 8149 https://www.mdpi.com/1422-0067/21/21/8149

Fenz et al. Biophysical Journal (2017), 112, 2245-6 https://doi.org/10.1016/j.bpj.2017.04.014

Monzel et al. Soft Matter (2016), 12, 4755-68 https://doi.org/10.1039/c6sm00412a

Monzel et al. Journal of Physics D: Applied Physics (2016), 49, 243002 https://doi.org/10.1088/0022-3727/49/24/243002

Monzel et al. Nature Communications (2015), 6:8162https://doi.org/10.1038/ncomms9162

Schmidt et al. Physical Review X (2014), 4, 021023 https://doi.org/10.1103/PhysRevX.4.021023

Monzel et al. Soft Matter (2012), 8, 6128-38 https://doi.org/10.1039/C2SM07458C

Monzel et al. ChemPhysChem (2009), 10, 2828-38 https://doi.org/10.1002/cphc.200900645

 

• Single Molecule Tracking of Molecular Motors 

Single Molecule Tracking enables to follow the motion of single molecules (or particles) with ~ 30 nm spatial resolution. Hence, this technique enables us to peer into the inner workings of the cell. A highly interesting example to investigate is the motion of molecular motors, which move along intracellular filaments such as actin or tubulin, and transport nutrients or neurotransmitters in vesicles from the cell centre towards it periphery. In our group we develop the technique of single molecule tracking further and investigate different aspects of this transport: on the one hand, we test novel approaches to label the molecules (e.g. via quantum dots) and use state-of-the art optics to increase the spatial resolution during tracking. On the other hand, we examine and characterize the motion of molecular motors, which play an important role in neurodegenerative diseases. To this end, we develop bioimage data analyses routines to classify different modes of their motion.      

Debayle et al. Biomaterials (2019)

 

• Cell Signaling

Berger et al. Small (2021),2101678

Gülcüler Balta et al. Cell Reports (2019), 29, 2295-2306 

 

• Cell Migration (in Hematopoietic Stem and Progenitor Cells, T-Cells, Cancer Cells)

Ohta, Monzel et al. Scientific Reports (2018), 8, 10630  https://doi.org//10.1038/s41598-018-28750-x

Monzel et al. Scientific Reports (2018), 8, 1841, https://doi.org//10.1038/s41598-018-19557-x

Burk et al. Scientific Reports (2015), 5, 9370 https://doi.org/10.1038/srep09370

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