Contact-mediated signaling enables disorder-driven transitions in cellular assemblies

Spontaneous generation of persistent activity in diffusively coupled cellular assemblies

The spontaneous generation of electrical activity underpins a number of essential physiological processes, and is observed even in tissues where specialized pacemaker cells have not been identified. The emergence of periodic oscillations in diffusively coupled assemblies of excitable and electrically passive cells (which are individually incapable of sustaining autonomous activity) has been suggested as a possible mechanism underlying such phenomena. In this paper we investigate the dynamics of such assemblies in more detail by considering simple motifs of coupled electrically active and passi…

Flags, Landscapes and Signaling: Contact-mediated inter-cellular interactions enable plasticity in fate determination driven by positional information

Multicellular organisms exhibit a high degree of structural organization with specific cell types always occurring in characteristic locations. The conventional framework for describing the emergence of such consistent spatial patterns is provided by Wolpert's "French flag" paradigm. According to this view, intra-cellular genetic regulatory mechanisms use positional information provided by morphogen concentration gradients to differentially express distinct fates, resulting in a characteristic pattern of differentiated cells. However, recent experiments have shown that suppression of inter-cel…

Simulating Organogenesis in COMSOL: Cell-based Signaling Models

Most models of biological pattern formation are simulated on continuous domains even though cells are discrete objects that provide internal boundaries to the diffusion of regulatory components. In our previous papers on simulating organogenesis in COMSOL (Germann et al COMSOL Conf Procedings 2011; Menshykau and Iber, COMSOL Conf Proceedings 2012) we discussed methods to efficiently solve signaling models on static and growing continuous domains. Here we discuss COMSOL-based methods to study spatio-temporal signaling models at cellular resolution with subcellular compartments, i.e. cell membra…

Understanding the principles of pattern formation driven by Notch signaling by integrating experiments and theoretical models

Notch signaling is an evolutionary conserved cell-cell communication pathway. Besides regulating cell-fate decisions at an individual cell level, Notch signaling coordinates the emergent spatiotemporal patterning in a tissue through ligand-receptor interactions among transmembrane molecules of neighboring cells, as seen in embryonic development, angiogenesis, or wound healing. Due to its ubiquitous nature, Notch signaling is also implicated in several aspects of cancer progression, including tumor angiogenesis, stemness of cancer cells and cellular invasion. Here, we review experimental and co…

Roles of Diffusion Dynamics and Molecular Concentration Gradients in Cellular Differentiation and Three-Dimensional Tissue Development

Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research avenues in disease modeling and regenerative medicine but also have ignited investigation into important aspects of molecular diffusion in 3D cellular architectures. This paper describes fundamental mechanics of diffusion with equations for modeling these dynamic processes under a variety of scenarios in 3D cellular tissue constructs. The effects of these diffusion processes and resultant concentration gradients are described i…

形态发生素调控的细胞间接触介导信号传导可驱动脊椎动物体节分割的转变过程

Morphogen-regulated contact-mediated signaling between cells can drive the transitions underlying body segmentation in vertebrates

本文提出一种统一机制，将受体-配体耦合的细胞间相互作用与形态发生素梯度相结合，再现了脊椎动物体节发生中从同步振荡、行波到活动停止及体节样模式出现的完整动力学转变序列。