ContactDr. Leif Dehmelt >
Phone: +49 (231) 755 7057
Prof. Dr. Perihan Nalbant
Phone: +49 (201) 183 3206
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.
Min Wu (2017). Pulses and waves of contractility.
J Cell Biol.
Cells permanently have to adapt their shape to their environment. Therefore, they use a dynamic actin cytoskeleton, which is regulated by a complex network of signaling molecules. The research groups of Leif Dehmelt and Perihan Nalbant (University Duisburg-Essen) identified a mechanism that enables a cellular sense of touch via local pulses of the signaling molecule Rho.
25 October 2017
Our sense of touch is central to perform even the simplest tasks – especially in darkness, when we cannot rely on our visual senses. The ability of touching something is not just passive, but is instead a very active process, in which we carefully adapt our movements to our sensory experiences. For example, if we want to know, if an object is hard or soft, we try to squeeze it with our hands.
The Dehmelt and Nalbant (University Duisburg-Essen) labs identified a mechanism, by which human cells can squeeze the material they interact with, in order to probe its elastic properties. This active squeezing process is controlled by a cellular signal network that generates an activity pulse of a signaling molecule, the GTPase Rho. This pulse first amplifies its activity and then inhibits itself after a short time delay. Such systems, that combine self-amplification and self-inhibition to trigger activity pulses, are called “excitable systems”. They are widely observed in nature, most prominently in the action potentials that propagate activity waves in neurons or in the heart muscle. By experimental augmentation of activity amplification, the researchers were also able to generate such propagating waves of the amplified signal molecule and the associated cellular squeezing behavior inside individual human cells.
So, what might be the significance of this active squeezing process? Interestingly, the researchers found that the frequency of squeezing pulses was modulated by the elasticity of the cells environment. This suggests that this active process could be used by the cells to probe their direct surrounding – similarly to our careful movements if we need to perform tasks in the dark. Individual cells usually do not have a visual sense and therefore have to majorly rely on their sense of touch to navigate through their environment. This tactile navigation process, in which cells also adapt their intrinsic programs in response to their environment, is thought to play an important role in the development of multicellular organisms and certain diseases, including cancer progression. There is certainly still a lot to be done to better understand the cell’s sense of touch, and the research from the Dehmelt and Nalbant labs now sheds light on some of its mysteries.
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 act as a molecular switch. 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 with 100 times increased speed. Bright and warm colours represent high activity levels of Rho.