The unifying theme of my research has been the use of tools and concepts from physics to address biological questions with strong focus on the understanding and prevention of cardiac diseases, which is a main cause of death in the modern society. I aim to develop and implement sophisticated analysis and quantification methods to study living systems and its dynamic functional processes with focus on diseases, maturity and its correlation to mechanosensitivity in cells and tissues.
I focus on the analysis of spatiotemporal and time-sensitive cell topology and signaling dynamics that interconnect the microscopic and macroscopic scales. Through these efforts I employ biology inspired materials, such as stimulus responsive hydrogels in combination with sophisticated computational analysis methods, i.e. three dimensional Delaunay triangulation algorithms to map and extract detailed cellular spatiotemporal signaling responses in single cells and tissues.
More specifically my research can be categorized as follows:
Signal Transduction in Cells and Tissues
Three-dimensional cell geometry controls excitable membrane signaling in Dictyostelium cells
M. Hörning and T. Shibata
BioRxiv, 278853, 2018 - doi : 10.1101/278853
Brief Summary: ''... Using a novel method of three-dimensional analysis of the entire cell membrane of Dictyostelium cells, we found that PtdInsP3 domains can propagate persistently in any direction on the entire plasma membrane, while their propagation direction and speed are governed by the geometry of the cell. This study opens more general questions about how the system geometry and spatiotemporal signaling interact to control pattern dynamics. ...''
Dynamics of spatiotemporal line defects and chaos control in complex excitable systems
M. Hörning*, F. Blanchard, A. Isomura and K. Yoshikawa
Scientific Reports, 7, 7757, 2017 - doi : 10.1038/s41598-017-08011-z
Brief Summary: ''... We show the spatiotemporal dynamics of line defects in rotating spiral waves. We combined a novel signaling over-sampling technique with a multi-dimensional Fourier analysis, showing that line defects can translate, merge, collapse and form stable singularities with even and odd parity while maintaining a stable oscillation of the spiral wave in the tissue. ...''
Excitable Signal Transduction Induces Both Spontaneous and Directional Cell Asymmetries in the Phosphatidylinositol Lipid Signaling System for Eukaryotic Chemotaxis
M. Nishikawa*, M. Hörning, M. Ueda and T. Shibata*
Biophysical Journal, 106, 3, 723-734, 2014 - doi : 10.1016/j.bpj.2013.12.023
Brief Summary: ''... Spatiotemporal dynamics of the phosphatidylinositol 3,4,5-trisphosphate (PIP3) is analyzed in Dictyostelium cells. It is shown that spontaneous activation of PIP3-enriched domains is generated by an intrinsic excitable system and how cells achieve high sensitivity to and robust coordination of the downstream activation that allows chemotactic behavior in the noisy environment. ...''
Mechanosensitive Processes in Cells and Tissues
Dynamic Mechano-Regulation of Myoblast Cells on Supramolecular Hydrogels Cross-Linked by Reversible Host-Guest Interactions
M. Hörning§, M. Nakahata§, P. Linke, A. Yamamoto, M. Veschgini, S. Kaufmann, Y. Takashima, A. Harada and M. Tanaka*
Scientific Reports, 7, 7760, 2017 - doi : 10.1038/s41598-017-07934-x
Brief Summary: ''... We apply a new class of revirsible rigidity switching hydrogels cross-linked by supramolecular host-guest interactions to actively control cells. In this study, the morphological dynamics of C2C12 myoblast in response to changes in substrate stiffness was observed and quantified in real time exemplarily. Actin depolarization dynamics as well as cellular responses are tracked over time. ...''
Negative Curvature and Control of Excitable Biological Media
M. Hörning and E. Entechva
Bottom-Up Self-Organization in Supramolecular Soft Matter, Principles and Prototypical Examples of Recent Advances, Springer Series in Materials Science, 217, Pages: 305, 2015 (book chapter) - doi : 10.1007/978-3-319-19410-3
Brief Summary: ''... Active and passive control of excitability in cardiac tissue are exemplarily reviewed by using rigidity controllable gels and tissue boundary shaping polymers. It is illustrated how the knowledge of tissue boundaries can be utilized to control excitation patterns, with relevance to the treatment of cardiac diseases. Further, new ways for active control of excitation patterns by light (optogenetics) and the influence of the substrate rigidity on the tissue morphology and signaling dynamics during development of cardiac tissue is discussed. ...''
Rigidity-matching between cells and the extracellular matrix leads to the stabilization of cardiac conduction
M. Hörning, S. Kidoaki, T. Kawano, and K. Yoshikawa
Biophysical Journal, 102, 379–387, 2012 - doi : 10.1016/j.bpj.2011.12.018
Brief Summary: ''...We found that myocardial conduction is significantly promoted when the rigidity of the cell culture environment matches that of the cardiac cells (ETissue = EECM = 12 kPa). The stability of spontaneous target wave activity and calcium transient alternans in high frequency-paced tissue were both enhanced when the cell substrate and cell tissue showed the same rigidity. We conclude that rigidity matching in cell-to-substrate interactions critically improves cardiomyocyte-tissue synchronization, suggesting that mechanical coupling plays an essential role in the dynamic activity of the beating heart. ...''
Pattern Formation in Excitable Biological Systems
Negative Curvature Boundaries as Wave Emitting Sites for the Control of Biological Excitable Media
P. Bittihn*, M. Hörning and S. Luther
Physical Review Letters, 109, 118106, 2012 - doi : 10.1103/PhysRevLett.109.118106
Brief Summary: ''... On the basis of a bidomain description, a unified theory for the electric-field-induced depolarization of the substrate near curved boundaries of generalized shapes is provided, resulting in the localized recruitment of control sites. The findings are confirmed in experiments on cardiomyocyte cell cultures and supported by two-dimensional numerical simulations on a cross section of a rabbit ventricle. ...''
Termination of pinned vortices by high-frequency wave trains in heartlike excitable media with anisotropic fiber orientation
Physical Review E, 86, 031912, 2012 - doi : 10.1103/PhysRevE.86.031912
Brief Summary: ''... The basic dependence of the conduction velocities of planar waves and waves around curved obstacles as a function of anisotropy through numerical simulations of excitable media that mimic the fiber orientation in a real heart is investigated. This knowledge is used to explain the unpinning of anchored spiral waves by high-frequency wave trains in an anisotropic excitable medium. A nonmonotonic relationship between the maximum unpinning period and the obstacle radius depending on the fiber orientation is observed, where the formation of unwanted secondary pinned vortices or chaotic waves is seen over a wide range of parameters.. ...''
Celestial Dynamics of Saturn's Outer Ring SystemPublications that resulted from my time as a Master student:
Cassini Dust Measurements at Enceladus and Implications for the Origin of the E Ring
F. Spahn, J. Schmidt, N. Albers, M. Hörning, M. Makuch, M. Seiss, S. Kempf, R. Srama, V. Dikarev, S. Helfert, G. Moragas-Klostermeyer, A.V. Krivov, M. Sremcevic, A.J. Tuzzolino, T. Economou and E. Grün
Science, 311, 1416, 2006, - doi : 10.1126/science.1121375
Brief Summary: ''In this study, we investigate the micron-sized dust particle distrubution around Enceladus, a moon in Saturn's E-ring with cryo-vulcanic activity. Realistic simulations are compared with data collected during Cassini’s close flyby of Enceladus on 14 July 2005 by the High Rate Detector of the Cosmic Dust Analyzer. The dust impact rate peaked about 1 minute before the closest approach of the spacecraft to the moon. This asymmetric signature is consistent with a locally enhanced dust production in the south polar region of Enceladus...''
E ring dust sources: Implications from Cassinis's dust measurements
F. Spahn, N. Albers, M. Hörning, S. Kempf, A.V. Krivov, M. Makuch, J. Schmidt, und M. Seiß
Planetary and Space Science, 54, 9-10, 1024-1032, 2006 - doi : 10.1016/j.pss.2006.05.022
Brief Summary: ''... The impact-generated dust contributions of the other E ring satellites is estimated and significant differences in the dust ejection efficiency by two projectile families—the E ring particles (ERPs) and the interplanetary dust particles (IDPs) is found. Together with the Enceladus south-pole source, the ERP impacts play a crucial role in the inner region, whereas the IDP impacts dominate the particle production in the outer E ring, possibly accounting for its large radial extent. ...''