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Research

Research Concept

The “Cell Morphodynamics” group studies how cells develop their complex shape. We particularly focus on the mecha­nisms that underlie the organization of dynamic, fibrous structures that are collectively called the cytoskeleton. To gain insight into those mecha­nisms, we first identify key system components via screening technologies. We then interrogate causalities between those components by combining acute activity perturbation and live-cell imaging. On the basis of those experiments, we build mathematical models of the spatio-temporal system dynamics, which help us to generate new, testable hypotheses.

Current Research

Self-organization of cytoskeletal dynamics

The emergence of cell shape can be perceived as a self-organizing process, in which dynamic, local interactions between mol­ecules lead to pattern formation at the scale of cells. The cytoskeleton takes an im­por­tant role in this process, due to its ability to translate patterns of signal network activity into patterns of intracellular forces to shape the cell. In our studies, we find that the cytoskeleton does not only transduce patterns, but is instead a central component of pattern formation based on reciprocal interplay with its regulators.

Spatio-temporal organization of cell contraction: "A sense of touch for individual cells"

In the context of our studies on cell contractility, we uncovered a self-organizing mechanism that leads to the spontaneous emergence of local pulses and propagating waves of the cytoskeletal regulator Rho (Video 1) [1]. Our experimental analysis showed that Rho amplifies its own activity by recruiting its activator GEF-H1 and that it inhibits its activity via time-delayed activation of myosins and associated RhoGAPs. Furthermore, Rho activity oscillations were modulated by matrix elasticity, showing that extracellular mechanical cues are coupled with signal network dynamics to control cell contractility. Thus, cells use contractility pulses to locally squeeze the plasma membrane to probe the elasticity of their surroundings and they use this in­for­mation to modulate their behavior. Individual cells therefore have a sense of touch that uses an active probing mechanism that is based on the local, subcellular control of signal network activity.

© Leif Dehmelt​/​TU Dort­mund

Video 1: Propagation of self-amplified and self-inhibited activity that controls the contractility of the cell’s plasma membrane. Here, the signal molecule is the small GTPase Rho, which can exist in an active or inactive state. Specifically, Rho regulates cell contraction by activation of a molecular motor called myosin. The video shows a time-lapse of a single, human cancer cell. Bright and warm colors represent high activity levels of Rho.

Relevant Literature

[1] Graessl M, Koch J, Calderon A, Kamps D, Banerjee S, Mazel T, Schulze N, Jungkurth JK, Patwardhan R, Solouk D, Hampe N, Hoffmann B, Dehmelt L, Nalbant P (2017). An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns. J Cell Biol 21(14):5311-6.
doi: 10.1083/jcb.201706052.

Acute perturbation and activity measurements in living cells

To uncover mecha­nisms, how cellular structures are or­ga­nized in space and time, methods are required that enable direct monitoring and acute perturbation of key regulators. To reach this goal, we developed novel generic approaches to simultaneously analyze and modulate biochemical reactions inside living cells.

Protein interaction arrays in living cells

In particular, relations between multiple protein reactions have to be measured simultaneously inside individual cells to untangle complex signal networks. However, current technologies to analyze protein reactions in cells are limited by the small number of markers that can be distinguished via mi­cros­co­py. To break this barrier, we developed miniaturized protein arrays that allow simultaneous monitoring of multiple protein interactions inside individual living cells (Figure 1) [2]. We are currently applying this technology to study signal networks that control cell shape changes.

Figure 1: Protein arrays inside living cells. Bait presenting artificial receptor constructs (bait-PARCs) transfer an antibody surface pattern into an ordered array of intracellular bait proteins. The interaction of a labeled prey protein with multiple bait proteins is monitored inside living cells via mi­cros­co­py.

Relevant Literature

[2] Gandor S, Reisewitz S, Venkatachalapathy M, Arrabito G, Reibner M, Schröder H, Ruf K, Niemeyer CM, Bastiaens PI, Dehmelt L (2013). A protein-interaction array inside a living cell. Angew Chem Int Ed Engl 52(18):4790-4.
doi: 10.1002/anie.201209127.

"Molecular Activity Painting": Switch-like, light-con­trolled perturbations inside living cells

To induce acute and prolonged perturbations of protein activities in the plasma membrane we developed methods based on chemically-induced dimerization and photochemically-induced targeting to immobilized artificial receptors to directly “paint” stable network perturbations in living cells (Video 2) [3]. To combine those perturbations with activity measurements, we developed TIRF-based methods to measure the activity of the major Rho GTPases Rac1, Cdc42 and RhoA. Using these tools, we directly investigated perturbation response relationships in the spatio-temporal processing of cell contractility signaling.

© Leif Dehmelt​/​TU Dort­mund

Video 2: Molecular activity painting of the letter “N” via ~1µm wide lines of the Rho activitor GEF-H1 (left panel). Plasma membrane localization of GEF-H1 induced the new formation of dynamic, myosin-based contractile structures (middle panel). Right panel: combined channels.

Relevant Literature

[3] Chen X, Venkatachalapathy M, Kamps D, Weigel S, Kumar R, Orlich M, Garrecht R, Hirtz M, Niemeyer CM, Wu YW, Dehmelt L. (2017). "Molecular-Activity Painting": Switch-like, Light-Con­trolled Perturbations inside Living Cells. Angew Chem Int Ed Engl 21(14):5311-6.
doi: 10.1002/anie.201611432

Location & approach

The campus of TU Dort­mund Uni­ver­sity is located close to interstate junction Dort­mund West, where the Sauerlandlinie A 45 (Frankfurt-Dort­mund) crosses the Ruhrschnellweg B 1 / A 40. The best interstate exit to take from A 45 is "Dort­mund-Eichlinghofen" (closer to Cam­pus Süd), and from B 1 / A 40 "Dort­mund-Dorstfeld" (closer to Cam­pus Nord). Signs for the uni­ver­si­ty are located at both exits. Also, there is a new exit before you pass over the B 1-bridge leading into Dort­mund.

To get from Cam­pus Nord to Cam­pus Süd by car, there is the connection via Vo­gel­pothsweg/Baroper Straße. We recommend you leave your car on one of the parking lots at Cam­pus Nord and use the H-Bahn (suspended monorail system), which conveniently connects the two campuses.

TU Dort­mund Uni­ver­sity has its own train station ("Dort­mund Uni­ver­si­tät"). From there, suburban trains (S-Bahn) leave for Dort­mund main station ("Dort­mund Hauptbahnhof") and Düsseldorf main station via the "Düsseldorf Airport Train Station" (take S-Bahn number 1, which leaves every 20 or 30 minutes). The uni­ver­si­ty is easily reached from Bochum, Essen, Mülheim an der Ruhr and Duis­burg.

You can also take the bus or subway train from Dort­mund city to the uni­ver­si­ty: From Dort­mund main station, you can take any train bound for the Station "Stadtgarten", usually lines U41, U45, U 47 and U49. At "Stadtgarten" you switch trains and get on line U42 towards "Hombruch". Look out for the Station "An der Palmweide". From the bus stop just across the road, busses bound for TU Dort­mund Uni­ver­sity leave every ten minutes (445, 447 and 462). Another option is to take the subway routes U41, U45, U47 and U49 from Dort­mund main station to the stop "Dort­mund Kampstraße". From there, take U43 or U44 to the stop "Dort­mund Wittener Straße". Switch to bus line 447 and get off at "Dort­mund Uni­ver­si­tät S".

The H-Bahn is one of the hallmarks of TU Dort­mund Uni­ver­sity. There are two stations on Cam­pus Nord. One ("Dort­mund Uni­ver­si­tät S") is directly located at the suburban train stop, which connects the uni­ver­si­ty directly with the city of Dort­mund and the rest of the Ruhr Area. Also from this station, there are connections to the "Technologiepark" and (via Cam­pus Süd) Eichlinghofen. The other station is located at the dining hall at Cam­pus Nord and offers a direct connection to Cam­pus Süd every five minutes.

The AirportExpress is a fast and convenient means of transport from Dort­mund Airport (DTM) to Dort­mund Central Station, taking you there in little more than 20 minutes. From Dort­mund Central Station, you can continue to the uni­ver­si­ty campus by interurban railway (S-Bahn). A larger range of in­ter­na­tio­nal flight connections is offered at Düsseldorf Airport (DUS), which is about 60 kilometres away and can be directly reached by S-Bahn from the uni­ver­si­ty station.

The facilities of TU Dort­mund Uni­ver­sity are spread over two campuses, the larger Cam­pus North and the smaller Cam­pus South. Additionally, some areas of the uni­ver­si­ty are located in the adjacent "Technologiepark".

Site Map of TU Dort­mund Uni­ver­sity (Second Page in English).