Quantitative Biology - Cell Behavior Publications (50)


Quantitative Biology - Cell Behavior Publications

Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance - yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time dependent. Here, we use a recently-developed model to obtain predictions for the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic. Read More

Background: The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. Read More

For various species of biological cells, experimental observations indicate the existence of universal distributions of the cellular size, scaling relations between the cell-size moments and simple rules for the cell-size control. We address a class of models for the control of cell division, and present the steady state distributions. By introducing concepts such as effective force and potential, we are able to address the appearance of scaling collapse of different distributions and the connection between various moments of the cell-size. Read More

The dispersal of cells from an initially constrained location is a crucial aspect of many physiological phenomena ranging from morphogenesis to tumour spreading. In such processes, the way cell-cell interactions impact the motion of single cells, and in turn the collective dynamics, remains unclear. Here, the spreading of micro-patterned colonies of non-cohesive cells is fully characterized from the complete set of individual trajectories. Read More

Biological functions are typically performed by groups of cells that express predominantly the same genes, yet display a continuum of phenotypes. While it is known how one genotype can generate such non-genetic diversity, it remains unclear how different phenotypes contribute to the performance of biological function at the population level. We developed a microfluidic device to simultaneously measure the phenotype and chemotactic performance of tens of thousands of individual, freely-swimming Escherichia coli as they climbed a gradient of attractant. Read More

Bacteria tightly regulate and coordinate the various events in their cell cycles to duplicate themselves accurately and to control their cell sizes. Growth of Escherichia coli, in particular, follows a relation known as Schaechter 's growth law. This law says that the average cell volume scales exponentially with growth rate, with a scaling exponent equal to the time from initiation of a round of DNA replication to the cell division at which the corresponding sister chromosomes segregate. Read More

From biofilm and colony formation in bacteria to wound healing and embryonic development in multicellular organisms, groups of living cells must often move collectively. While considerable study has probed the biophysical mechanisms of how eukaryotic cells generate forces during migration, little such study has been devoted to bacteria, in particular with regard to the question of how bacteria generate and coordinate forces during collective motion. This question is addressed here for the first time using traction force microscopy. Read More

In population biology, the Allee dynamics refer to negative growth rates below a critical population density. In this Letter, we study a reaction-diffusion (RD) model of population growth and dispersion in one dimension, which incorporates the Allee effect in both the growth and mortality rates. In the absence of diffusion, the bifurcation diagram displays regions of both finite population density and zero population density, i. Read More

Cell migration in morphogenesis and cancer metastasis typically involves interplay between different cell types. We construct and study a minimal, one-dimensional model comprised of two different motile cells with each cell represented as an active elastic dimer. The interaction between the two cells via cadherins is modeled as a spring that can rupture beyond a threshold force as it undergoes dynamic loading via the attached motile cells. Read More

Cell polarization and directional cell migration can display random, persistent and oscillatory dynamic patterns. However, it is not clear if these polarity patterns can be explained by the same underlying regulatory mechanism. Here, we show that random, persistent and oscillatory migration accompanied by polarization can simultaneously occur in populations of melanoma cells derived from tumors with different degrees of aggressiveness. Read More

100 years after Smoluchowski introduces his approach to stochastic processes, they are now at the basis of mathematical and physical modeling in cellular biology: they are used for example to analyse and to extract features from large number (tens of thousands) of single molecular trajectories or to study the diffusive motion of molecules, proteins or receptors. Stochastic modeling is a new step in large data analysis that serves extracting cell biology concepts. We review here the Smoluchowski's approach to stochastic processes and provide several applications for coarse-graining diffusion, studying polymer models for understanding nuclear organization and finally, we discuss the stochastic jump dynamics of telomeres across cell division and stochastic gene regulation. Read More

We construct a model of cell reprogramming (the conversion of fully differentiated cells to a state of pluripotency, known as induced pluripotent stem cells, or iPSCs) which builds on key elements of cell biology viz. cell cycles and cell lineages. Although reprogramming has been demonstrated experimentally, much of the underlying processes governing cell fate decisions remain unknown. Read More

Cell differentiation is an important process in living organisms. Differentiation is mostly based on binary decisions with the progenitor cells choosing between two specific lineages. The differentiation dynamics have both deterministic and stochastic components. Read More

In the present work we simulate the basic two-dimensional dynamics of swarming E. coli bacteria on the surface of a moderately soft agar plate. Individual bacteria are modelled by self-propelled ridged bodies (agents), which interact with each other only through inelastic collision and with the highly viscous environment through damping forces. Read More

Recent biological research has sought to understand how biochemical signaling pathways, such as the mitogen-activated protein kinase (MAPK) family, influence the migration of a population of cells during wound healing. Fisher's Equation has been used extensively to model experimental wound healing assays due to its simple nature and known traveling wave solutions. This partial differential equation with independent variables of time and space cannot account for the effects of biochemical activity on wound healing, however. Read More

We present a weakly coupled map lattice model for patterning that explores the effects exerted by weakening the local dynamic rules on model biological and artificial networks composed of two-state building blocks (cells). To this end, we use two cellular automata models based on: (i) a smooth majority rule (model I) and (ii) a set of rules similar to those of Conway's Game of Life (model II). The normal and abnormal cell states evolve according with local rules that are modulated by a parameter $\kappa$. Read More

This article presents an algorithm for the evaluation of organelles' movements inside of an unmodified live cell. We used a time-lapse image series obtained using wide-field bright-field photon transmission microscopy as an algorithm input. The benefit of the algorithm is the application of the R\'enyi information entropy, namely a variable called a point information gain, which enables to highlight the borders of the intracellular organelles and to localize the organelles' centers of mass with the precision of one pixel. Read More

Mounting evidence for the role of oxidative stress in the degeneration of articular cartilage after an injurious impact requires our modeling & simulation efforts to temporarily shift from just describing the effect of mechanical stress and inflammation on osteoarthritis (OA). The hypothesis that the injurious impact causes irreversible damage to chondrocyte mitochondria, which in turn increase their production of free radicals, affecting their energy production and their ability to rebuild the extracellular matrix, has to be modeled and the processes quantified in order to further the understanding of OA, its causes, and viable treatment options. The current article presents a calibrated model that captures the damage oxidative stress incurs on the cell viability, ATP production, and cartilage stability in a cartilage explant after a drop-tower impact. Read More

We develop a theoretical approach that uses physiochemical kinetics modelling to describe cell population dynamics upon progression of viral infection in cell culture, which results in cell apoptosis (programmed cell death) and necrosis (direct cell death). Several model parameters necessary for computer simulation were determined by reviewing and analyzing available published experimental data. By comparing experimental data to computer modelling results, we identify the parameters that are the most sensitive to the measured system properties and allow for the best data fitting. Read More

In this work we introduce a stochastic model to describe directional changes in the movement of swimming bacteria. We use the probability density function (PDF) of turn angles, measured on tumbling \textit{E. coli} wild-type, to build a Langevin equation for the deflection of the bacterial body swimming in isotropic media. Read More

We derive the constitutive equations of an active polar gel from a model for the dynamics of elastic molecules that link polar elements. Molecular binding kinetics induces the fluidization of the material, giving rise to Maxwell viscoelasticity and, provided that detailed balance is broken, to the generation of active stresses. We give explicit expressions for the transport coefficients of active gels in terms of molecular properties, including nonlinear contributions on the departure from equilibrium. Read More

We report an experimental study of the influences of the fixed charge and bulk ionic concentrations on the conduction of biological ion channels, and we consider the results within the framework of the ionic Coulomb blockade model of permeation and selectivity. Voltage clamp recordings were used to investigate the Na$^+$/Ca$^{2+}$ anomalous mole fraction effect (AMFE) exhibited by the bacterial sodium channel NaChBac and its mutants. Site-directed mutagenesis was used to study the effect of either increasing or decreasing the fixed charge in their selectivity filters for comparison with the predictions of the Coulomb blockade model. Read More

Chemotaxis and haptotaxis have been a main theme in the macroscopic study of bacterial and cellular motility. In this work we investigate the influence these processes have on the shape and motility of fast migrating cells. We note that despite their biological and modelling differences, the cells exhibit many similarities in their migration. Read More

This is a Commentary in $Physics~Today$ on the novel review process developed by the biology journal $eLife$, with the suggestion that it be adopted by physics journals. Read More

The pathogenesis and progression of many tumors, including hematologic malignancies is highly dependent on enhanced lipogenesis. De novo fatty-acid synthesis permits accelerated proliferation of tumor cells by providing structural components to build the membranes. It may also lead to alterations of physicochemical properties of the formed membranes, which can have an impact on signaling or even increase resistance to drugs in cancer cells. Read More

Phototaxis is an important reaction to light displayed by a wide range of motile microorganisms. Flagellated eukaryotic microalgae in particular, like the model organism Chlamydomonas reinhardtii, steer either towards or away from light by a rapid and precisely timed modulation of their flagellar activity. Cell steering, however, is only the beginning of a much longer process which ultimately allows cells to determine their light exposure history. Read More

A continuum model for epithelial tissue mechanics is formulated from cell level mechanical ingredients and morphogenetic cell dynamics, including cell shape changes and cell rearrangements. The model is capable of dealing with finite deformation, and uses stress and deformation tensors that can be compared with experimental data. Using the model, we uncover the dynamical behaviour that underlies passive relaxation and active contraction-elongation of a tissue. Read More

It is well known that population sizes increase exponentially during balanced growth. Concomitantly, at the single-cell level, the sizes of individual cells themselves increase exponentially; the single-cell exponential growth-rate also determines the statistics of cell size and cell division time distributions. Seeking an integrated perspective of microbial growth dynamics under balanced conditions, we formulate a theoretical framework that takes into account observables at both single-cell and population scales. Read More

Building on the striking similarity between the structure of the spindle during mitosis in living cells and nematic textures in confined liquid crystals, we use a continuum model of two-dimensional nematic liquid crystal droplets, to examine the physical aspects of cell division. The model investigates the interplay between bulk elasticity of the microtubule assembly, described as a nematic liquid crystal, and surface elasticity of the cell cortex, modelled as a bounding flexible membrane, in controlling cell shape and division. The centrosomes at the spindle poles correspond to the cores of the topological defects required to accommodate nematic order in a closed geometry. Read More

The highly conserved spindle assembly checkpoint (SAC) ensures that the sister chromatids of the duplicated genome are not separated and distributed to the spindle poles before all chromosomes have been properly linked to the microtubules of the mitotic spindle. Biochemically, the SAC delays cell cycle progression by preventing activation of the anaphase-promoting complex (APC/C) or cyclosome; whose activation by Cdc20 is required for sister-chromatid separation, which marks the transition into anaphase. In response to activation of the checkpoint, various species control the activity of both APC/C and Cdc20. Read More

Using a popular vertex-based model to describe a spatially disordered planar epithelial monolayer, we examine the relationship between cell shape and mechanical stress at the cell and tissue level. Deriving expressions for stress tensors starting from an energetic formulation of the model, we show that the principal axes of stress for an individual cell align with the principal axes of shape, and we determine the bulk effective tissue pressure when the monolayer is isotropic at the tissue level. Using simulations for a monolayer that is not under peripheral stress, we fit parameters of the model to experimental data for Xenopus embryonic tissue. Read More

Intracellular Ca signals represent a universal mechanism of cell function. Messages carried by Ca are local, rapid, and powerful enough to be delivered over the thermal noise. A higher signal to noise ratio is achieved by a cooperative action of Ca release channels such as IP3 receptors or ryanodine receptors arranged in clusters or release units containing a few to several hundred release channels. Read More

Cells crawling through tissues migrate inside a complex fibrous environment called the extracellular matrix (ECM), which provides signals regulating motility. Here we investigate one such well-known pathway, involving mutually antagonistic signalling molecules (small GTPases Rac and Rho) that control the protrusion and contraction of the cell edges (lamellipodia). Invasive melanoma cells were observed migrating on surfaces with topography (array of posts), coated with adhesive molecules (fibronectin, FN) by Park et al. Read More

Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. Read More

Numerous biological approaches are available to characterise the mechanisms which govern the formation of human embryonic stem cell (hESC) colonies. To understand how the kinematics of single and pairs of hESCs impact colony formation, we study their mobility characteristics using time-lapse imaging. We perform a detailed statistical analysis of their speed, survival, directionality, distance travelled and diffusivity. Read More

In this work, we introduce a facile procedure to graft a thin graphitic C3N4 (g-C3N4) layer on aligned TiO2 nanotube arrays (TiNT) by one-step chemical vapor deposition (CVD) approach. This provides a platform to enhance the visible-light response of TiO2 nanotubes for antimicrobial applications. The formed g- C3N4/TiNT binary nanocomposite exhibits excellent bactericidal efficiency against E. Read More

Collective cell motility plays central roles in various biological phenomena such as inflammatory response, wound healing, cancer metastasis and embryogenesis. These are biological demonstrations of the unjamming transition. However, contradictory to the typical density-driven jamming processes in particulate assemblies, cellular systems often get unjammed in highly packed, sometimes overcrowding tissue environments. Read More

A Markovian lattice model for photoreceptor cells is introduced to describe the growth of mosaic patterns on fish retina. The radial stripe pattern observed in wild-type zebrafish is shown to be selected naturally during the retina growth, against the geometrically equivalent, circular stripe pattern. The mechanism of such dynamical pattern selection is clarified on the basis of both numerical simulations and theoretical analyses, finding that successive emergence of local defects plays a critical role to realize the wild-type pattern. Read More

It is now well established that nearby beating pairs of eukaryotic flagella or cilia typically synchronize in phase. A substantial body of evidence supports the hypothesis that hydrodynamic coupling between the active filaments, combined with waveform compliance, provides a robust mechanism for synchrony. This elastohydrodynamic mechanism has been incorporated into `bead-spring' models in which flagella are represented by microspheres tethered by radial springs as internal forces drive them about orbits. Read More

A central question in developmental biology is how size and position are determined. The genetic code carries instructions on how to control these properties in order to regulate the pattern and morphology of structures in the developing organism. Transcription and protein translation mechanisms implement these instructions. Read More

Cyanobacteria forming one-dimensional filaments are paradigmatic model organisms of the transition between unicellular and multicellular living forms. Under nitrogen limiting conditions, in filaments of the genus Anabaena, some cells differentiate into heterocysts, which lose the possibility to divide but are able to fix environmental nitrogen for the colony. These heterocysts form a quasi-regular pattern in the filament, representing a prototype of patterning and morphogenesis in prokaryotes. Read More

Recent research has shown that motile cells can adapt their mode of propulsion depending on the environment in which they find themselves. One mode is swimming by blebbing or other shape changes, and in this paper we analyze a class of models for movement of cells by blebbing and of nano- robots in a viscous fluid at low Reynolds number. At the level of individuals, the shape changes comprise volume exchanges between connected spheres that can control their separation, which are simple enough that significant analytical results can be obtained. Read More

How the cells break symmetry and organize their edge activity to move directionally is a fun- damental question in cell biology. Physical models of cell motility commonly rely on gradients of regulatory factors and/or feedback from the motion itself to describe polarization of edge activity. Theses approaches, however, fail to explain cell behavior prior to the onset of polarization. Read More

We propose and investigate a delayed model that studies the relationship between HIV and the immune system during the natural course of infection and in the context of antiviral treatment regimes. Sufficient criteria for local asymptotic stability of the infected and viral free equilibria are given. An optimal control problem with time delays both in state variables (incubation delay) and control (pharmacological delay) is then formulated and analyzed, where the objective consists to find the optimal treatment strategy that maximizes the number of uninfected $CD4^{+}$ T cells as well as CTL immune response cells, keeping the drug therapy as low as possible. Read More

Myriad experiments have identified an important role for $\rm CD8^+$ T cell response mechanisms in determining recovery from influenza A virus infection. Animal models of influenza infection further implicate multiple elements of the immune response in defining the dynamical characteristics of viral infection. To date, influenza virus models, while capturing particular aspects of the natural infection history, have been unable to reproduce the full gamut of observed viral kinetic behaviour in a single coherent framework. Read More

We consider self-tolerance and its failure -autoimmunity- in a minimal mathematical model of the idiotypic network. A node in the network represents a clone of B-lymphocytes and its antibodies of the same idiotype which is encoded by a bitstring. The links between nodes represent possible interactions between clones of almost complementary idiotype. Read More

Genetically identical microbial cells typically display significant variability in every measurable property. In particular, highly abundant proteins - which can determine cellular behavior - exhibit large variability in copy number among individuals. Their distribution has a universal shape common to different proteins and microorganisms; the same distribution shape is measured both in populations and in single-cell temporal traces. Read More

Septins are guanine nucleotide-binding proteins that are conserved from fungi to humans. Septins assemble into heterooligomeric complexes and higher-order structures with key roles in various cellular functions including cell migration and division. The mechanisms by which septins assemble and interact with other cytoskeletal elements like actin remain elusive. Read More

The Cellular Potts Model (CPM) is a lattice based modeling technique which is widely used for simulating cellular patterns such as foams or biological tissues. Despite its realism and generality, the standard Monte Carlo algorithm used in the scientific literature to evolve this model preserves connectivity of cells on a limited range of simulation temperature only. We present a new algorithm in which cell fragmentation is forbidden for all simulation temperatures. Read More