Invasion Speed Research Articles

Collective cell migration during human mammary gland organoid morphogenesis.

Organ morphogenesis is driven by cellular migration patterns, which become accessible for observation in organoid cultures. We demonstrate here that mammary gland organoids cultured from human primary cells, exhibit oscillatory and collective migration patterns during their development into highly branched structures, as well as persistent rotational motion within the developed alveoli. Using high-resolution live-cell imaging, we observed cellular movement over the course of several days and subsequently characterized the underlying migration pattern by means of optical flow algorithms. Confined by the surrounding collagen matrix, characteristic correlated back-and-forth movements emerge due to a mismatch between branch invasion and cell migration speeds throughout the branch invasion phase. In contrast, alveolar cells exhibit continuous movement in the same direction. By modulating cell-cell adhesions, we identified collective migration as a prerequisite for sustaining these migration patterns both during the branching elongation process and after alveolus maturation.

Tracking a killer shrimp: Dikerogammarus villosus invasion dynamics across Europe

AbstractAimInvasive alien species are a growing problem worldwide due to their ecological, economic and human health impacts. The “killer shrimp” Dikerogammarus villosus is a notorious invasive alien amphipod from the Ponto‐Caspian region that has invaded many fresh and brackish waters across Europe. Understandings of large‐scale population dynamics of highly impactful invaders such as D. villosus are lacking, inhibiting predictions of impact and efficient timing of management strategies. Hence, our aim was to assess trends and dynamics of D. villosus as well as its impacts in freshwater rivers and streams.LocationEurope.MethodsWe analysed 96 European time series between 1994 and 2019 and identified trends in the relative abundance (i.e. dominance %) of D. villosus in invaded time series, as well as a set of site‐specific characteristics to identify drivers and determinants of population changes and invasion dynamics using meta‐regression modelling. We also looked at the spread over space and time to estimate the invasion speed (km/year) of D. villosus in Europe. We investigated the impact of D. villosus abundance on recipient community metrics (i.e. abundance, taxa richness, temporal turnover, Shannon diversity and Pielou evenness) using generalized linear models.ResultsPopulation trends varied across the time series. Nevertheless, community dominance of D. villosus increased over time across all time series. The frequency of occurrences (used as a proxy for invader spread) was well described by a Pareto distribution, whereby we estimated a lag phase (i.e. the time between introduction and spatial expansion) of approximately 28 years, followed by a gradual increase before new occurrences declined rapidly in the long term. D. villosus population change was associated with decreased taxa richness, community turnover and Shannon diversity.Main ConclusionOur results show that D. villosus is well‐established in European waters and its abundance significantly alters ecological communities. However, the multidecadal lag phase prior to observed spatial expansion suggests that initial introductions by D. villosus are cryptic, thus signalling the need for more effective early detection methods.

The Tumor Invasion Paradox in Cancer Stem Cell-Driven Solid Tumors

Cancer stem cells (CSCs) are key in understanding tumor growth and tumor progression. A counterintuitive effect of CSCs is the so-called tumor growth paradox: the effect where a tumor with a higher death rate may grow larger than a tumor with a lower death rate. Here we extend the modeling of the tumor growth paradox by including spatial structure and considering cancer invasion. Using agent-based modeling and a corresponding partial differential equation model, we demonstrate and prove mathematically a tumor invasion paradox: a larger cell death rate can lead to a faster invasion speed. We test this result on a generic hypothetical cancer with typical growth rates and typical treatment sensitivities. We find that the tumor invasion paradox may play a role for continuous and intermittent treatments, while it does not seem to be essential in fractionated treatments. It should be noted that no attempt was made to fit the model to a specific cancer, thus, our results are generic and theoretical.

Tumor–neuron interactions: A novel concept contributor to glioblastoma invasion

Tumor–neuron interactions: A novel concept contributor to glioblastoma invasion

Dynamic Species Distribution Modeling Reveals the Pivotal Role of Human-Mediated Long-Distance Dispersal in Plant Invasion

Simple SummaryUnderstanding biological invasion mechanisms is crucial to design effective management strategies preventing their impacts on ecosystems. If the role of long-distance dispersal and age-dependent fecundity in plant invasion speed has been characterized in theory, empirical support is still rare given the difficulty to jointly fit demographic and spread parameters of dynamic models to available data. We proposed a statistical model to fit such parameters to heterogeneous observations collected across space and time. We can directly test hypotheses on the importance of various mechanisms in a past invasion. We demonstrated the potential of this method by determining the roles of human-mediated long-distance dispersal and age-dependent fecundity in the invasion of the shrub Plectranthus barbatus in South Africa. Our model revealed a massive wave of spread driven by human-mediated long-distance dispersal and originating from the cities of first introduction. The species completed its invasion of all favorable areas a few years after, in the mid-1990s. Without human-mediated long-distance dispersal, the maximum population would have been obly 30% of the current population. The delayed reproductive maturity explained the invasion lag phase. It highlights the importance of early eradication of weedy horticultural alien plants around urban areas to hamper the invasive spread.Plant invasions generate massive ecological and economic costs worldwide. Predicting their spatial dynamics is crucial to the design of effective management strategies and the prevention of invasions. Earlier studies highlighted the crucial role of long-distance dispersal in explaining the speed of many invasions. In addition, invasion speed depends highly on the duration of its lag phase, which may depend on the scaling of fecundity with age, especially for woody plants, even though empirical proof is still rare. Bayesian dynamic species distribution models enable the fitting of process-based models to partial and heterogeneous observations using a state-space modeling approach, thus offering a tool to test such hypotheses on past invasions over large spatial scales. We use such a model to explore the roles of long-distance dispersal and age-structured fecundity in the transient invasion dynamics of Plectranthus barbatus, a woody plant invader in South Africa. Our lattice-based model accounts for both short and human-mediated long-distance dispersal, as well as age-structured fecundity. We fitted our model on opportunistic occurrences, accounting for the spatio-temporal variations of the sampling effort and the variable detection rates across datasets. The Bayesian framework enables us to integrate a priori knowledge on demographic parameters and control identifiability issues. The model revealed a massive wave of spatial spread driven by human-mediated long-distance dispersal during the first decade and a subsequent drastic population growth, leading to a global equilibrium in the mid-1990s. Without long-distance dispersal, the maximum population would have been equivalent to 30% of the current equilibrium population. We further identified the reproductive maturity at three years old, which contributed to the lag phase before the final wave of population growth. Our results highlighted the importance of the early eradication of weedy horticultural alien plants around urban areas to hamper and delay the invasive spread.

Competition between cell types under cell cycle regulation with apoptosis

Competition between different cell types plays a crucial role in bacterial ecology, developmental biology, and tumor growth. We study how cells compete in 2D by using both a mean field theory and particle-based simulations. We employ a mechanical model that incorporates a stylized form of cell cycle regulation to control cell division events. This is extended to treat multiple cell types with different rates of programed cell death (apoptosis) and characteristic cell-cycle control pressures. Analytic predictions for the invasion speed and the coexistence line are in agreement with simulations. Synchronization in the cell division/apoptosis events can emerge, leading to oscillations in pressure and cell-cycle activity. We also study the invasion or elimination of small (pre)cancerous colonies. We show how a Laplace pressure at the colony interface, here controlled by differential cell adhesion, shifts the coexistence line; there are cell types that can invade when starting from a large colony but will be eliminated if the colony is small.

Invasion of Aleurodicus Rugioperculatus Martin in Assam: Posing Threat to Coconut Growers

Aleurodicus rugioperculatus Martin has invaded NER India in 2018 and established already in many districts of lower Assam and is alarmingly spreading to new districts owing to the inadequate domestic quarantine. The pest has been detected for the first time in Biswanath district of Lower Brahmaputra Valley Zone of Assam in May, 2019. Variation in speed of invasion has been noticed in different zones depending on the mode of dispersal of the pest. Rainfall had no impact on short-distance dispersal of the pest. However, rainfall-deficient months of 2018 and low rainfall days of 2019 had some impact on its arrival and establishment. The pest is likely to affect the coconut economy in future. Extensive survey in the NER India for assessing crop loss due to the invasion and enforcement of strict domestic quarantine in inter-state borders are the urgent need of the hour.

Glioblastoma hijacks neuronal mechanisms for brain invasion

Glioblastomas are incurable tumors infiltrating the brain. A subpopulation of glioblastoma cells forms a functional and therapy-resistant tumor cell network interconnected by tumor microtubes (TMs). Other subpopulations appear unconnected, and their biological role remains unclear. Here, we demonstrate that whole-brain colonization is fueled by glioblastoma cells that lack connections with other tumor cells and astrocytes yet receive synaptic input from neurons. This subpopulation corresponds to neuronal and neural-progenitor-like tumor cell states, as defined by single-cell transcriptomics, both in mouse models and in the human disease. Tumor cell invasion resembled neuronal migration mechanisms and adopted a Lévy-like movement pattern of probing the environment. Neuronal activity induced complex calcium signals in glioblastoma cells followed by the de novo formation of TMs and increased invasion speed. Collectively, superimposing molecular and functional single-cell data revealed that neuronal mechanisms govern glioblastoma cell invasion on multiple levels. This explains how glioblastoma's dissemination and cellular heterogeneity are closely interlinked.

Simple and automatic monitoring of cancer cell invasion into an epithelial monolayer using label-free holographic microscopy

The invasiveness of cancer cells describes the metastasizing capability of a primary tumor. The straightforward detection and quantification of cancer cell invasion are important to predict the survival rate of a cancer patient and to test how anti-cancer compounds influence cancer progression. Digital holographic microscopy based M4 Holomonitor (HM) is a technique that allows the label-free monitoring of cell morphological and kinetical parameters in real-time. Here, a fully confluent epithelial monolayer derived from the African green monkey kidney (Vero) on a gelatin-coated surface was established, then HeLa cells were seeded on top of the monolayer, and their behavior was monitored for 24 h using HM. Several cancer cells showing invasiveness were detected during this period, while other HeLa cells did not show any signs of aggressivity. It was demonstrated that the invasion of single cancer cells is soundly observable and also quantifiable through monitoring parameters such as phase shift, optical volume, area, and motility, which parameters can easily be obtained and processed automatically. Based on the experimental data, the invasion speed of cancer cells entering the epithelial layer can be defined as the shrinking of detected single-cell volume per unit time. The invasion speed and its correlation with cell migration parameters were analyzed in depth. A clear linear relationship between migration and invasion speed was found, cancer cells with stronger migration have slower invasion speed. These results not only describe the effect of how cancer cells invade the underlying monolayer in contrast to non-invasive HeLa cells, but could help in future research to optimize drugs affecting cell invasibility in a fully automated, label-free and high-throughput manner.

Invasion Speed of Predator in a Lattice Dynamical System

This article studies the invasion dynamics of a lattice dynamical system with predator-prey type nonlinearity, which models that the predator invades the habitat of the prey. The system does not generate monotone semiflows and can not be studied by the well known conclusions. By constructing proper auxiliary equations, we obtain the rough invasion speed of the predator that initially occupies a habitat of finite size.

Rapid bentonite-cement-oil hydration: Implications to fluid loss control

Conventional particulate additives fail to control drilling fluid losses into large-aperture fractures. The separate injections of a bentonite-cement-oil suspension and water can cause rapid hydration, swelling and hardening to effectively plug fractures. This experimental study investigates underlying processes and implications in view of optimal fluid flow control in fractures. Results identify several concurrent hydro-chemo-mechanical coupled processes: capillarity-driven water invasion; cement hydration and the release of Ca2+ and OH− ions; bentonite contractive aggregation and increased hydrophilicity; enlarged inter-aggregate pores that facilitate fluid flow; oil pressurization leading to the formation of oil-filled opening mode discontinuities that facilitate oil escape towards free draining boundaries, and calcium silicate hydrate formation and growth resulting in hardening. The hydration of bentonite-cement-oil suspensions proceeds several times faster than in bentonite-oil suspensions. The optimal mixture should balance competing requirements between flowability, water invasion speed, swelling pressure and plug strength.

Pore-scale simulation of two-phase flow and oxygen reactive transport in gas diffusion layer of proton exchange membrane fuel cells: Effects of nonuniform wettability and porosity

Enhancing oxygen transport and reducing water flooding in the gas diffusion layer (GDL) of proton exchange membrane fuel cells are important for improving cell performance. In this study, a pore-scale model based on the lattice Boltzmann method is proposed, which considers two-phase flow, oxygen diffusion and electrochemical reaction in the GDL. The invasion speed of the water into the GDL is determined by the water generation rate and correspondingly the oxygen consumption rate. The model is then adopted to study effects of wettability and porosity distribution on the liquid water saturation, oxygen concentration and current density. The results demonstrate that while reducing the total saturation in the GDL is important, decreasing the local saturation near the microporous layer (MPL)/GDL interface is also crucial for enhancing cell performance. It is found that GDL with locally enhanced hydrophobicity at the MPL/GDL interface or gradually increased porosity from the GDL bottom to the GDL top can improve cell performance. Particularly, by delicately designing the GDL porosity, the current density can be considerably increased by 201%. The developed pore-scale model provides a useful tool for understanding the underlying multiphase reactive transport processes in GDL and designing the microscopic structures of GDL.

Acoustic Bioprinting of Patient-Derived Organoids for Predicting Cancer Therapy Responses.

Cancer models, which are biologically representative of patient tumors, can predict the treatment responses and help determine the most appropriate cancer treatment for individual patients. Here, a point-of-care testing system called acoustically bioprinted patient-derived microtissues (PDMs) that can model cancer invasion and predict treatment response in individual patients with colorectal cancer (CRC), is reported. The PDMs are composed of patient-derived colorectal tumors and healthy organoids which can be precisely arranged by acoustic bioprinting approach for recapulating primary tissue's architecture. Particularly, these tumor organoids can be efficiently generated and can apprehend histological, genomic, and phenotypical characteristics of primary tumors. Consequently, these PDMs allow physiologically relevant in vitro drug (5-fluorouracil) screens, thus predicting the paired patient's responses to chemotherapy. A correlation between organoid invasion speed and normalized spreading speed of the paired patients is further established. It provides a quantitative indicator to help doctors make better decisions on ultimate anus-preserving operation for extremely low CRC patients. Thus, by combing acoustic bioprinting and organoid cultures, this method may open an avenue to establish complex 3D tissue models for precision and personalized medicine.

The Spreading Speed and the Existence of Planar Waves for a Class of Predator-prey System with Nonlocal Diffusion

In this paper, we study a predator-prey system with general response function and nonlocal diffusion in high dimensional space and investigate the propagation properties of its solution. More precisely, we study the invasion speed of the predator into habitat of the aborigine prey and obtain the existence of the planar waves by constructing the upper and lower solutions. Finally, we present some numerical simulations to support our results.

Comparing the effects of linear and one-term Ogden elasticity in a model of glioblastoma invasion.

Our modelling of brain mechanics is based on observations of Budday and colleagues [6], who analyzed the elastic properties of human brain tissue samples under multiple loading modes. Using these data, Budday et al. determined a realistic constitutive model for brain tissue mechanics. In these studies, they found that compression and shear responses were best modelled by a non-linear one-term Ogden elasticity model, although other elasticity models are possible as well. Here we analyze the role of the elasticity model of brain tissue on the invasion speed of glioma and the resulting tissue deformation (mass effect). We present a one dimensional continuum model that couples cell dynamics to tissue mechanics. Since the mechanics of glioma-compromised brain tissue is not clear, for comprehensive studies, we incorporate both elastic and viscoelastic versions of two brain tissue elasticity models - the commonly employed linear model and the experimentally determined one-term Ogden model. For each elasticity model we identify travelling wave solutions in one dimension and calculate the corresponding invasion speeds. We find that the invasion speed is, in fact, independent of the chosen elasticity model. However, the deformations of the brain tissue, and resulting stress, between the linear and one-term Ogden models are drastically different: the Ogden model shows two orders of magnitude less deformation and three orders of magnitude less stress as compared to the linear model. Such a discrepancy might be relevant when looking at glioma-induced health complications. Statement of significanceCancers arising from glial cells, known as gliomas, form in the spine and the brain. The spread of glioma is not fully understood, although recent studies have highlighted the role of tissue mechanics as a main factor in the invasion process. We present a one dimensional continuum model framework of glioma invasion that incorporates proliferation and invasion of glioma cells, as well as mass effects by coupling cell dynamics to tissue mechanics. We explore both elastic and viscoelastic versions of two brain tissue elasticity models - the commonly employed linear model and the experimentally determined one-term Ogden model. This is the first time the one-term Ogden model has been incorporated into a model of glioma invasion. We show that although the choice of elasticity model does not affect the invasion speed, the deformation and stress generated in the tissue are significantly different with the Ogden model producing three orders of magnitude less deformation and stress as compared to the linear model. Such a discrepancy might be relevant when looking at glioma-induced health complications.

Invasion into remnant instability: a case study of front dynamics

We study the invasion of an unstable state by a propagating front in a peculiar but generic situation where the invasion process exhibits a remnant instability. Here, remnant instability refers to the fact that the spatially constant invaded state is linearly unstable in any exponentially weighted space in a frame moving with the linear invasion speed. Our main result is the nonlinear asymptotic stability of the selected invasion front for a prototypical model coupling spatio-temporal oscillations and monotone dynamics. We establish stability through a decomposition of the perturbation into two pieces: one that is bounded in the weighted space and a second that is unbounded in the weighted space but which converges uniformly to zero in the unweighted space at an exponential rate. Interestingly, long-time numerical simulations reveal an apparent instability in some cases. We exhibit how this instability is caused by round-off errors that introduce linear resonant coupling of otherwise non-resonant linear modes, and we determine the accelerated invasion speed.

A nonlocal population model for the invasion of Canada goldenrod.

A mathematical model for the population invasion of Canada goldenrod is proposed, with two reproductive modes, yearly periodic time delay and spatially nonlocal response caused by the influence of wind on the seeds. Under suitable conditions, we obtain the existence of the rightward and leftward invasion speeds and their coincidence with the minimal speeds of time periodic traveling waves. Furthermore, the invasion speeds are finite if the dispersal kernel of seeds is exponentially bounded and infinite if dispersal kernel is exponentially unbounded.

Probing the mechanism of external fluids invasion of nanopores in fractured tight sandstone reservoir

The oilfield development process is accompanied by reservoir damage, which affects the reservoir permeability and reduces production. In this study, the mechanism of external-fluid invasion was analyzed to maintain oil-well productivity. The characteristics of the damage caused by external fluids to tight sandstone reservoirs were examined via scanning electron microscopy and high-pressure mercury-invasion experiments. Then, seepage models for fluids in the nanopores of tight sandstone reservoirs were established to investigate the effects of the natural fracture parameters and fluid properties on the seepage characteristics and damage mechanism of fractured tight sandstone reservoirs. The results indicated that the damage rates of water-based drilling fluid, oil-based drilling fluid, guar-gum fracturing fluid, and slick-water fracturing fluid for the natural core of tight sandstone are 53.20%, 33.87%, 23.64%, and 19.10%, respectively. The proportion of nanopores in fractured tight sandstone reservoirs ranges from 44.62% to 62.45%. The invasion of external fluids leads to a reduction in the permeability as well as the number of microfractures and their lengths. The changes in permeability barely affect the seepage characteristics of the fluid in the nanopores. The reductions in the lengths and number of microfractures change the connectivity of the entire flow space, affecting the seepage characteristics. The effect of the lengths of the microfractures is more significant than that of the number of microfractures. Additionally, the invasion speed of the external fluids has the most significant effect on the seepage characteristics. A higher viscosity of the external fluids corresponds to less damage to the nanopores. Drilling fluid causes less damage to nanopores than fracturing fluid does. The recovery of fractured tight oil reservoirs with nanopores can be enhanced by reducing the degree of external-fluid invasion.

Spectral stability of pattern-forming fronts in the complex Ginzburg–Landau equation with a quenching mechanism

We consider pattern-forming fronts in the complex Ginzburg–Landau equation with a traveling spatial heterogeneity which destabilises, or quenches, the trivial ground state while progressing through the domain. We consider the regime where the heterogeneity propagates with speed c just below the linear invasion speed of the pattern-forming front in the associated homogeneous system. In this situation, the front locks to the interface of the heterogeneity leaving a long intermediate state lying near the unstable ground state, possibly allowing for growth of perturbations. This manifests itself in the spectrum of the linearisation about the front through the accumulation of eigenvalues onto the absolute spectrum associated with the unstable ground state. As the quench speed c increases towards the linear invasion speed, the absolute spectrum stabilises with the same rate at which eigenvalues accumulate onto it allowing us to rigorously establish spectral stability of the front in . The presence of unstable absolute spectrum poses a technical challenge as spatial eigenvalues along the intermediate state no longer admit a hyperbolic splitting and standard tools such as exponential dichotomies are unavailable. Instead, we projectivise the linear flow, and use Riemann surface unfolding in combination with a superposition principle to study the evolution of subspaces as solutions to the associated matrix Riccati differential equation on the Grassmannian manifold. Eigenvalues can then be identified as the roots of the meromorphic Riccati–Evans function, and can be located using winding number and parity arguments.

TAMI-24. INHIBITION OF GBM INVASION BY THE Α-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID (AMPA) GLUTAMATE RECEPTOR ANTAGONIST PERAMPANEL

Abstract BACKGROUND Extensive tumor cell invasion within the brain represents a major problem for effective treatment of glioblastomas (GBMs). The invasive processes can be divided into three types: Collective cell invasion, perivascular infiltration, and single-cell invasion into the brain parenchyma. GBM cells can form synapses with neural cells pointing at an extensive communication network between brain and GBM cells which can be mediated via the metabolites Glutamine and Glutamate both needed for GBM cell proliferation. In this context, it has been shown in preclinical models that Perampanel, an antiepileptic agent, functioning as non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, has an inhibitory effect on GBM growth. To delineate how Perampanel affects GBM invasion, we utilised a highly characterized 3D GBM-brain organoid invasion model where single-cell invasion was studied in real-time following Perampanel treatment. METHODS A brain coculture model, consisting of rat brain organoids expressing various markers of the human adult brain, where confronted with GFP-labelled tumor cells. By using time-lapse confocal microscopy, we quantified single-cell invasion patterns and speed of invasion using two glioma stem cell models (BG5 and BG7). RESULTS Perampanel treatment significantly reduces tumor cell invasion into the brain organoids with the strongest effect seen in the most invasive GBM (BG5). The single-tumor cell invasion ratio was reduced by 72 % compared to the control (p= 0.0033). In contrast, collective cell invasion was reduced by 19 % (p= 0.028). Statistical analysis was performed using an unpaired sample t-test. CONCLUSION The AMPA glutamate receptor antagonist Perampanel significantly inhibits GBM invasion, suggesting an important role of the glutamate-glutamine cycle between the GBM cells and neurons in the invasion process. Moreover, this communication and exchange of metabolites seem to be more prominent where single GBM cells invade into the brain parenchyma compared to areas where collective invasion take place.