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:
Control and Analysis of 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.. ...''
Mathematical and Computational Quantification of Cell and Tissue Dynamics
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. ...''
Elucidation of Mechanosensitive Processes of Cells and Tissues
Live cell tracking of symmetry break in actin cytoskeleton triggered by abrupt changes in micromechanical environments
S. Inoue§, V. Frank§, M. Hörning§, S. Kaufmann, H. Y. Yoshikawa, J. P. Madsen, A. L. Lewis, S. P. Armes and M. Tanaka*
Biomaterials Science, 3, 12, 1539-1544, 2015
- doi : 10.1039/c5bm00205b
Brief Summary: ''... The morphological dynamics of myoblast (C2C12) cells in response to an abrupt change in the substrate elasticity was monitored by live cell imaging. The remodeling of actin cytoskeletons could be monitored by means of transient transfection with LifeAct-GFP and the dynamic changes in the orientational order of actin filaments were quantified. The critical role that acto-myosin complexes play in the morphological transition was verified by the treatment of cells with myosin II inhibitor (blebbistatin) and the fluorescence localization of focal adhesion contacts. ...''
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. ...''