Coupled Dynamics in Phenotype and Tissue Spaces Shape the Three-Dimensional Cancer Invasion.

The metastasis of solid tumors hinges on cancer cells navigating through complex three-dimensional tissue environments, characterized by mechanical heterogeneity and biological diversity. This process is closely linked to the dynamic migration behavior exhibited by cancer cells, which dictates the invasiveness of tumors. In our study, we investigate tumor spheroids composed of breast cancer cells embedded in three-dimensional (3D) collagen matrices.

Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells.

The coordinated movement of cell collectives is essential for normal epithelial tissue development, maintenance, and cancer progression. Here, we report on a minimal 3D extracellular matrix (ECM) system wherein both invasive collective migration (ICM) and rotational collective migration (RCM) arise spontaneously from individually seeded epithelial cells of mammary and hepatic origin, regardless of whether they express adherens junctions, and lead to ductal-like and acinar-like structures, respectively. Quantitative microscopy and cellular Potts modeling reveal that initial differences in cell protrusion dynamics and matrix-remodeling localization generate RCM and ICM behavior in confining 3D ECM.

Annihilation dynamics during spiral defect chaos revealed by particle models.

Pair-annihilation events are ubiquitous in a variety of spatially extended systems and are often studied using computationally expensive simulations. Here we develop an approach in which we simulate the pair-annihilation of spiral wave tips in cardiac models using a computationally efficient particle model. Spiral wave tips are represented as particles with dynamics governed by diffusive behavior and short-ranged attraction.

Boolean modelling in plant biology.

Signalling and genetic networks underlie most biological processes and are often complex, containing many highly connected components. Modelling these networks can provide insight into mechanisms but is challenging given that rate parameters are often not well defined. Boolean modelling, in which components can only take on a binary value with connections encoded by logic equations, is able to circumvent some of these challenges, and has emerged as a viable tool to probe these complex networks.

A role for ethylene signaling and biosynthesis in regulating and accelerating CO - and abscisic acid-mediated stomatal movements in Arabidopsis.

Little is known about long-distance mesophyll-driven signals that regulate stomatal conductance. Soluble and/or vapor-phase molecules have been proposed. In this study, the involvement of the gaseous signal ethylene in the modulation of stomatal conductance in Arabidopsis thaliana by CO /abscisic acid (ABA) was examined.

The physics of heart rhythm disorders.

The global burden caused by cardiovascular disease is substantial, with heart disease representing the most common cause of death around the world. There remains a need to develop better mechanistic models of cardiac function in order to combat this health concern. Heart rhythm disorders, or arrhythmias, are one particular type of disease which has been amenable to quantitative investigation.

Predicting acute termination and non-termination during ablation of human atrial fibrillation using quantitative indices.

Termination of atrial fibrillation (AF), the most common arrhythmia in the United States, during catheter ablation is an attractive procedural endpoint, which has been associated with improved long-term outcome in some studies. It is not clear, however, whether it is possible to predict termination using clinical data. We developed and applied three quantitative indices in global multielectrode recordings of AF prior to ablation: average dominant frequency (ADF), spectral power index (SPI), and electrogram quality index (EQI).

Stochastic termination of spiral wave dynamics in cardiac tissue.

Rotating spiral waves are self-organized features in spatially extended excitable media and may play an important role in cardiac arrhythmias including atrial fibrillation (AF). In homogeneous media, spiral wave dynamics are perpetuated through spiral wave breakup, leading to the continuous birth and death of spiral waves, but have a finite probability of termination. In non-homogeneous media, however, heterogeneities can act as anchoring sources that result in sustained spiral wave activity.

Intermittent trapping of spiral waves in a cardiac model.

Spiral waves are found in many excitable systems and are thought to play a role in the incoherent electrical activation that underlies cardiac arrhythmias. It is well-known that spiral waves can be permanently trapped by local heterogeneities. In this paper, we demonstrate that spiral waves can also be intermittently trapped by such heterogeneities.

Deep dive into CO2-dependent molecular mechanisms driving stomatal responses in plants.

Recent advances are revealing mechanisms mediating CO-regulated stomatal movements in Arabidopsis, stomatal architecture and stomatal movements in grasses, and the long-term impact of CO on growth.

Coupling traction force patterns and actomyosin wave dynamics reveals mechanics of cell motion.

Motile cells can use and switch between different modes of migration. Here, we use traction force microscopy and fluorescent labeling of actin and myosin to quantify and correlate traction force patterns and cytoskeletal distributions in Dictyostelium discoideum cells that move and switch between keratocyte-like fan-shaped, oscillatory, and amoeboid modes. We find that the wave dynamics of the cytoskeletal components critically determine the traction force pattern, cell morphology, and migration mode.

Boolink: a graphical interface for open access Boolean network simulations and use in guard cell CO2 signaling.

Signaling networks are at the heart of almost all biological processes. Most of these networks contain large number of components, and often either the connections between these components are not known or the rate equations that govern the dynamics of soluble signaling components are not quantified. This uncertainty in network topology and parameters can make it challenging to formulate detailed mathematical models.

Three dimensional reconstruction to visualize atrial fibrillation activation patterns on curved atrial geometry.

Background: The rotational activation created by spiral waves may be a mechanism for atrial fibrillation (AF), yet it is unclear how activation patterns obtained from endocardial baskets are influenced by the 3D geometric curvature of the atrium or 'unfolding' into 2D maps. We develop algorithms that can visualize spiral waves and their tip locations on curved atrial geometries. We use these algorithms to quantify differences in AF maps and spiral tip locations between 3D basket reconstructions, projection onto 3D anatomical shells and unfolded 2D surfaces.

The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance.

Contact guidance is a major physical cue that modulates cancer cell morphology and motility, and is directly linked to the prognosis of cancer patients. Under physiological conditions, particularly in the three-dimensional (3D) extracellular matrix (ECM), the disordered assembly of fibers presents a complex directional bias to the cells. It is unclear how cancer cells respond to these noncoherent contact guidance cues.

Cellular memory in eukaryotic chemotaxis depends on the background chemoattractant concentration.

Cells of the social amoeba Dictyostelium discoideum migrate to a source of periodic traveling waves of chemoattractant as part of a self-organized aggregation process. An important part of this process is cellular memory, which enables cells to respond to the front of the wave and ignore the downward gradient in the back of the wave. During this aggregation, the background concentration of the chemoattractant gradually rises.

Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study.

[Figure: see text].

Cell dispersal by localized degradation of a chemoattractant.

Chemotaxis, the guided motion of cells by chemical gradients, plays a crucial role in many biological processes. In the social amoeba , chemotaxis is critical for the formation of cell aggregates during starvation. The cells in these aggregates generate a pulse of the chemoattractant, cyclic adenosine 3',5'-monophosphate (cAMP), every 6 min to 10 min, resulting in surrounding cells moving toward the aggregate.

Tissue topography steers migrating border cells.

Moving cells can sense and respond to physical features of the microenvironment; however, in vivo, the significance of tissue topography is mostly unknown. Here, we used border cells, an established model for in vivo cell migration, to study how chemical and physical information influences path selection. Although chemical cues were thought to be sufficient, live imaging, genetics, modeling, and simulations show that microtopography is also important.

Machine Learned Cellular Phenotypes in Cardiomyopathy Predict Sudden Death.

Rationale: Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside.

Objective: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes.

Methods And Results: We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing.