A rigid body framework for multi-cellular modelling

ABSTRACTMulti-cellular modelling, where tissues and organs are represented by a collection of individual interacting agents, is a well established field, encapsulating several different approaches. In particular, off-lattice models, which represent cells using points that are free to move in space, have been applied to numerous biological problems in both two and three dimensions. The fact that a cell can be represented by point objects is useful in a wide range of settings, particularly when large populations are involved. However, a purely point-based representation is not naturally equipped to deal with objects that inherently have length like cell boundaries or external membranes.In this paper we introduce a novel off-lattice modelling framework that exploits rigid body mechanics to represent cells using a collection of one-dimensional edges (rather than zero-dimensional points) in a viscosity-dominated system. The rigid body framework can be used, among other things, to represent cells as free moving polygons, to allow epithelial layers to smoothly interact with themselves, and to model rod shaped cells like bacteria. We demonstrate the value of our new framework by using it in these three applications, showing that this approach can replicate established results, as well as offer solutions to problems that limit the scope of current off-lattice multi-cellular models.

Molecular and Cellular Modelling of Salivary Gland Tumors Open New Landscapes in Diagnosis and Treatment

Salivary gland tumors are neoplasms affecting the major and minor salivary glands of the oral cavity. Their complex pathological appearance and overlapping morphological features between subtypes, pose major challenges in the identification, classification, and staging of the tumor. Recently developed techniques of three-dimensional culture and organotypic modelling provide useful platforms for the clinical and biological characterization of these malignancies. Additionally, new advances in genetic and molecular screenings allow precise diagnosis and monitoring of tumor progression. Finally, novel therapeutic tools with increased efficiency and accuracy are emerging. In this review, we summarize the most common salivary gland neoplasms and provide an overview of the state-of-the-art tools to model, diagnose, and treat salivary gland tumors.

Analysis of self-equilibrated networks through cellular modelling

Network equilibrium models represent a versatile tool for the analysis of interconnected objects and their relationships. They have been widely employed in both science and engineering to study the behaviour of complex systems under various conditions, including external perturbations and damage. In this paper, network equilibrium models are revisited through graph-theory laws and attributes with special focus on systems that can sustain equilibrium in the absence of external perturbations (self-equilibrium). A new approach for the analysis of self-equilibrated networks is proposed; they are modelled as a collection of cells, predefined elementary network units that have been mathematically shown to compose any self-equilibrated network. Consequently, the equilibrium state of complex self-equilibrated systems can be obtained through the study of individual cell equilibria and their interactions. A series of examples that highlight the flexibility of network equilibrium models are included in the paper. The examples attest how the proposed approach, which combines topological as well as geometrical considerations, can be used to decipher the state of complex systems.

Cellular modelling: experiments and simulation to develop a physiological model of G-protein control of muscarinic K + channels in mammalian atrial cells

The first model of G-protein–K ACh channel interaction was developed 14 years ago and then expanded to include both the receptor–G-protein cycle and G-protein–K ACh channel interaction. The G-protein–K ACh channel interaction used the Monod–Wyman–Changeux allosteric model with the idea that one K ACh channel is composed of four subunits, each of which binds one active G-protein subunit (G βγ ). The receptor–G-protein cycle used a previous model to account for the steady-state relationship between K ACh current and intracellular guanosine-5-triphosphate at various extracellular concentrations of acetylcholine (ACh). However, simulations of the activation and deactivation of K ACh current upon ACh application or removal were much slower than experimental results. This clearly indicates some essential elements were absent from the model. We recently found that regulators of G-protein signalling are involved in the control of K ACh channel activity. They are responsible for the voltage-dependent relaxation behaviour of K ACh channels. Based on this finding, we have improved the receptor–G-protein cycle model to reproduce the relaxation behaviour. With this modification, the activation and deactivation of K ACh current in the model are much faster and now fall within physiological ranges.