Quantitative Biology - Cell Behavior Publications (50)


Quantitative Biology - Cell Behavior Publications

Stress-induced glucocorticoid elevation is a highly conserved response among vertebrates. This facilitates stress adaptation and the mode of action involves activation of the intracellular glucocorticoid receptor leading to the modulation of target gene expression. However, this genomic effect is slow acting and, therefore, a role for glucocorticoid in the rapid response to stress is unclear. Read More

Signaling in enzymatic networks is typically triggered by environmental fluctuations, resulting in a series of stochastic chemical reactions, leading to corruption of the signal by noise. For example, information flow is initiated by binding of extracellular ligands to receptors, which is transmitted through a {cascade involving} kinase-phosphatase stochastic chemical reactions. For a class of such networks, we develop a general field-theoretic approach in order to calculate the error in signal transmission as a function of an appropriate control variable. Read More

It was shown in C. elegans that life-long treatments with low level of the prooxidant paraquat increased ROS, which then acted as the signal to slow down aging by activating the intrinsic apoptosis pathway. And deficiencies of the electron transport chain subunits increased longevity through similar mechanisms. Read More

Collective cell migration is a highly regulated process involved in wound healing, cancer metastasis and morphogenesis. Mechanical interactions among cells provide an important regulatory mechanism to coordinate such collective motion. Using a Self-Propelled Voronoi (SPV) model that links cell mechanics to cell shape and cell motility, we formulate a generalized mechanical inference method to obtain the spatio-temporal distribution of cellular stresses from measured traction forces in motile tissues and show that such traction-based stresses match those calculated from instantaneous cell shapes. Read More

Contact between particles and motile cells underpins a wide variety of biological processes, from nutrient capture and ligand binding, to grazing, viral infection and cell-cell communication. The window of opportunity for these interactions is ultimately determined by the physical mechanism that enables proximity and governs the contact time. Jeanneret et al. Read More

Intra-tumour phenotypic heterogeneity limits accuracy of clinical diagnostics and hampers the efficiency of anti-cancer therapies. Dealing with this cellular heterogeneity requires adequate understanding of its sources, which is extremely difficult, as phenotypes of tumour cells integrate hardwired (epi)mutational differences with the dynamic responses to microenvironmental cues. The later come in form of both direct physical interactions, as well as inputs from gradients of secreted signalling molecules. Read More

Information entropy is used to summarize transcriptome data, but ignoring zero count data contained them. Ignoring zero count data causes loss of information and sometimes it was difficult to distinguish between multiple transcriptomes. Here, we estimate Kolmogorov complexity of transcriptome treating zero count data and distinguish similar transcriptome data. Read More

We report a novel form of convection in suspensions of the bioluminiscent marine bacterium $Photobacterium~phosphoreum$. Suspensions of these bacteria placed in a chamber open to the air create persistent luminiscent plumes most easily visible when observed in the dark. These flows are strikingly similar to the classical bioconvection pattern of aerotactic swimming bacteria, which create an unstable stratification by swimming upwards to an air-water interface, but they are a puzzle since the strain of $P. Read More

While most processes in biology are highly deterministic, stochastic mechanisms are sometimes used to increase cellular diversity, such as in the specification of sensory receptors. In the human and Drosophila eye, photoreceptors sensitive to various wavelengths of light are distributed randomly across the retina. Mechanisms that underlie stochastic cell fate specification have been analysed in detail in the Drosophila retina. Read More

Collective cell migration is a hallmark of developmental and patho-physiological states, including wound healing and invasive cancer growth. The integrity of the expanding epithelial sheets can be influenced by extracellular cues, including cell-cell and cell-matrix interactions. We show the nano-scale topography of the extracellular matrix underlying epithelial cell layers can have a strong effect on the speed and morphology of the fronts of the expanding sheet triggering epithelial-mesenchymal transition (EMT). Read More

The aim of this work is to quantify the spatio-temporal dynamics of flow-driven amoeboid locomotion in small ($\sim$100 $\mu$m) fragments of the true slime mold \phys {\it polycephalum}. In this model organism, cellular contraction drives intracellular flows, and these flows transport the chemical signals that regulate contraction in the first place. As a consequence of these non-linear interactions, a diversity of migratory behaviors can be observed in migrating \phys fragments. Read More

Multicellular chemotaxis can occur via individually chemotaxing cells that are physically coupled. Alternatively, it can emerge collectively, from cells chemotaxing differently in a group than they would individually. We find that while the speeds of these two mechanisms are roughly the same, the precision of emergent chemotaxis is higher than that of individual-based chemotaxis for one-dimensional cell chains and two-dimensional cell sheets, but not three-dimensional cell clusters. Read More

Causal ordering of key events in the cell cycle is essential for proper functioning of an organism. Yet, it remains a mystery how a specific temporal program of events is maintained despite ineluctable stochasticity in the biochemical dynamics which dictate timing of cellular events. We propose that if a change of cell fate is triggered by the {\em time-integral} of the underlying stochastic biochemical signal, rather than the original signal, then a dramatic improvement in temporal specificity results. Read More

Hair cells, the sensory receptors of the internal ear, subserve different functions in various receptor organs: they detect oscillatory stimuli in the auditory system, but transduce constant and step stimuli in the vestibular and lateral-line systems. We show that a hair cell's function can be controlled experimentally by adjusting its mechanical load. By making bundles from a single organ operate as any of four distinct types of signal detector, we demonstrate that altering only a few key parameters can fundamentally change a sensory cell's role. Read More

A classic problem in microbiology is that bacteria display two types of growth behavior when cultured on a mixture of two carbon sources: in certain mixtures the bacteria consume the two carbon sources sequentially (diauxie) and in other mixtures the bacteria consume both sources simultaneously (co-utilization). The search for the molecular mechanism of diauxie led to the discovery of the lac operon and gene regulation in general. However, why microbes would bother to have different strategies of taking up nutrients remained a mystery. Read More

A sperm-driven micromotor is presented as cargo-delivery system for the treatment of gynecological cancers. This particular hybrid micromotor is appealing to treat diseases in the female reproductive tract, the physiological environment that sperm cells are naturally adapted to swim in. Here, the single sperm cell serves as an active drug carrier and as driving force, taking advantage of its swimming capability, while a laser-printed microstructure coated with a nanometric layer of iron is used to guide and release the sperm in the desired area by an external magnet and structurally imposed mechanical actuation, respectively. Read More

Collective motion of chemotactic bacteria as E. Coli relies, at the individual level, on a continuous reorientation by runs and tumbles. It has been established that the length of run is decided by a stiff response to temporal sensing of chemical cues along the pathway. Read More

Long-read sequencing has enabled the de novo assembly of several mammalian genomes, but with high cost in computing. Here, we demonstrated de novo assembly of mammalian genome using long reads in an efficient and inexpensive workstation. Read More

Robustness of spatial pattern against perturbations is an indispensable property of developmental processes for organisms, which need to adapt to changing environments. Although specific mechanisms for this robustness have been extensively investigated, little is known about a general mechanism for achieving robustness in reaction-diffusion systems. Here, we propose a buffered reaction-diffusion system, in which active states of chemicals mediated by buffer molecules contribute to reactions, and demonstrate that robustness of the pattern wavelength is achieved by the dynamics of the buffer molecule. Read More

We present a theory of flagellar synchronization in the green alga Chlamydomonas, using full treatment of flagellar hydrodynamics. We find that two recently proposed synchronization mechanisms, basal coupling and flagellar waveform compliance, stabilize anti-phase synchronization if operative in isolation. Their nonlinear superposition, however, stabilizes in-phase synchronization as observed in experiments. Read More

High hydrostatic pressure is commonly encountered in many environments, but the effects of high pressure on eukaryotic cells have been understudied. To understand the effects of hydrostatic pressure in the model eukaryote, Saccharomyces cerevisiae, we have performed quantitative experiments of cell division, cell morphology, and cell death under a wide range of pressures. We developed an automated image analysis method for quantification of the yeast budding index - a measure of cell cycle state - as well as a continuum model of budding to investigate the effect of pressure on cell division and cell morphology. Read More

Most of the calcium in the body is stored in bone. The rest is stored elsewhere, and calcium signalling is one of the most important mechanisms of information propagation in the body. Yet, many questions remain open. Read More

Advances in synthetic biology allow us to engineer bacterial collectives with pre-specified characteristics. However, the behavior of these collectives is difficult to understand, as cellular growth and division as well as extra-cellular fluid flow lead to complex, changing arrangements of cells within the population. To rationally engineer and control the behavior of cell collectives we need theoretical and computational tools to understand their emergent spatiotemporal dynamics. Read More

Stochastic exponential growth is observed in a variety of contexts, including molecular autocatalysis, nuclear fission, population growth, inflation of the universe, viral social media posts, and financial markets. Yet literature on modeling the phenomenology of these stochastic dynamics has predominantly focused on one model, Geometric Brownian Motion (GBM), which can be described as the solution of a Langevin equation with linear drift and linear multiplicative noise. Using recent experimental results on stochastic exponential growth of individual bacterial cell sizes, we motivate the need for a more general class of phenomenological models of stochastic exponential growth, which are consistent with the observation that the mean-rescaled distributions are approximately stationary at long times. Read More

Myxobacteria are social bacteria, that can glide in 2D and form counter-propagating, interacting waves. Here we present a novel age-structured, continuous macroscopic model for the movement of myxobacteria. The derivation is based on microscopic interaction rules that can be formulated as a particle-based model and set within the SOH (Self-Organized Hydrodynamics) framework. Read More

Cells exhibit qualitatively different behaviors on substrates with different rigidities. The fact that cells are more polarized on the stiffer substrate motivates us to construct a two-dimensional cell with the distribution of focal adhesions dependent on substrate rigidities. This distribution affects the forces exerted by the cell and thereby determines its motion. Read More

This paper investigates cells proliferation dynamics in small tumor cell aggregates using an individual based model (IBM). The simulation model is designed to study the morphology of the cell population and of the cell lineages as well as the impact of the orientation of the division plane on this morphology. Our IBM model is based on the hypothesis that cells are incompressible objects that grow in size and divide once a threshold size is reached, and that newly born cell adhere to the existing cell cluster. Read More

Chemotaxis, a basic and universal phenomenon among living organisms, directly controls the transport kinetics of active fluids such as swarming bacteria, but has not been considered when utilizing passive tracer to probe the nonequilibrium properties of such fluids. Here we present the first theoretical investigation of the diffusion dynamics of a chemoattractant-coated tracer in bacterial suspension, by developing a molecular dynamics model of bacterial chemotaxis. We demonstrate that the non-Gaussian statistics of full-coated tracer arises from the noises exerted by bacteria, which is athermal and exponentially correlated. Read More

Finding the origin of slow and infra-slow oscillations could reveal or explain brain mechanisms in health and disease. Here, we present a biophysically constrained computational model of a neural network where the inclusion of astrocytes introduced slow and infra-slow-oscillations, through two distinct mechanisms. Specifically, we show how astrocytes can modulate the fast network activity through their slow inter-cellular calcium wave speed and amplitude and possibly cause the oscillatory imbalances observed in diseases commonly known for such abnormalities, namely Alzheimer's disease, Parkinson's disease, epilepsy, depression and ischemic stroke. Read More

We consider the chemotaxis problem for a one-dimensional system. To analyze the interaction of bacteria and attractant we use a modified Keller-Segel model which accounts attractant absorption. To describe the system we use the chemotaxis sensitivity function, which characterizes nonuniformity of bacteria distribution. Read More

We introduce a simple mechanical model for adherent cells that quantitatively relates cell shape, internal cell stresses and cell forces as generated by an anisotropic cytoskeleton. We perform experiments on the shape and traction forces of different types of cells with anisotropic morphologies, cultured on microfabricated elastomeric pillar arrays. We demonstrate that, irrespectively of the cell type, the shape of the cell edge between focal adhesions is accurately described by elliptical arcs, whose eccentricity expresses the ratio between directed and isotropic stresses. Read More

Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond by reorganizing their cell-cell junctions and migrating directionally towards the sites of injury. Read More

The major biochemical networks of the living cell, the network of interacting genes and the network of biochemical reactions, are highly interdependent, however, they have been studied mostly as separate systems so far. In the last years an appropriate theoretical framework for studying interdependent networks has been developed in the context of statistical physics. Here we study the interdependent network of gene regulation and metabolism of the model organism Escherichia coli using the theoretical framework of interdependent networks. Read More

In this work we use a combination of statistical physics and dynamical systems approaches, to analyze the response to an antigen of a simplified model of the adaptive immune system, which comprises B, T helper and T regulatory lymphocytes. Results show that the model is remarkably robust against changes in the kinetic parameters, noise levels, and mechanisms that activate T regulatory lymphocytes. In contrast, the model is extremely sensitive to changes in the ratio between T helper and T regulatory lymphocytes, exhibiting in particular a phase transition, from a responsive to an immuno-suppressed phase, when the ratio is lowered below a critical value. Read More

During embryogenesis tissue layers continuously rearrange and fold into specific shapes. Developmental biology identified patterns of gene expression and cytoskeletal regulation underlying local tissue dynamics, but how actions of multiple domains of distinct cell types coordinate to remodel tissues at the organ scale remains unclear. We use in toto light-sheet microscopy, automated image analysis, and physical modeling to quantitatively investigate the link between kinetics of global tissue transformations and force generation patterns during Drosophila gastrulation. Read More

The theory of irreversible thermodynamics for arbitrarily curved lipid membranes is presented here. The coupling between elastic bending and irreversible processes such as intra-membrane lipid flow, intra-membrane phase transitions, and protein binding and diffusion is studied. The forms of the entropy production for the irreversible processes are obtained, and the corresponding thermodynamic forces and fluxes are identified. Read More

Associative learning is one of the key mechanisms displayed by living organisms in order to adapt to their changing environments. It was early recognized to be a general trait of complex multicellular organisms but also found in "simpler" ones. It has also been explored within synthetic biology using molecular circuits that are directly inspired in neural network models of conditioning. Read More

Many aquatic organisms exhibit remarkable abilities to detect and track chemical signals when foraging, mating and escaping. For example, the male copepod { \em T. longicornis} identifies the female in the open ocean by following its chemically-flavored trail. Read More

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