Many developmental processes in biology utilize Notch-Delta signaling to construct an ordered pattern of cellular differentiation. This signaling modality is based on nearest-neighbor contact, as opposed to the more familiar mechanism driven by the release of diffusible ligands. Here, exploiting this ``juxtacrine" property, we present an exact treatment of the pattern formation problem via a system

The small GTPases Rac and Rho are known to regulate eukaryotic cell shape, promoting front protrusion (Rac) or rear retraction (Rho) of the cell edge. Such cell deformation changes the contact and adhesion of cell to the extracellular matrix (ECM), while ECM signaling through integrin receptors also affects GTPase activity. We develop and investigate a model for this three-way feedback loop in 1D and

In this work we use a Discrete Markov Chain (DMC) approach combined with network centrality measures to identify and predict the location of active sites in globular proteins. To accomplish this, we use a three-dimensional network of protein Cα atoms as nodes connected through weighted edges which represent the varying interaction degree between protein's atoms. We compute the mean first passage time

The effects of internal adaptation dynamics on the self-organized aggregation of chemotactic bacteria are investigated by Monte Carlo (MC) simulations based on a two-stream kinetic transport equation coupled with a reaction-diffusion equation of the chemoattractant that bacteria produce. A remarkable finding is a nonmonotonic behavior of the peak aggregation density with respect to the adaptation time;

We introduce a Reed–Frost epidemic model with recursive contact tracing and asymptomatic transmission. This generalizes the branching-process model introduced by the authors in a previous work (Bulchandani et al 2021 Phys. Biol. 18 045004) to finite populations and general contact networks. We simulate the model numerically for two representative examples, the complete graph and the square lattice

Cancer is a set of genetic diseases that are driven by mutations. It was recently discovered that the temporal order of genetic mutations affects the cancer evolution and even the nature of the decease itself. The mechanistic origin of these observations, however, remain not well understood. Here we present a theoretical model for cancer initiation dynamics that allows us to quantify the impact of

Protein beta-2-microglobulin (β2m) is classically considered the causative agent of dialysis related amyloidosis, a conformational disorder that affects patients undergoing long-term hemodialysis. The wild type (WT) form, the ΔN6 structural variant, and the D76N mutant have been extensively used as model systems of β2m aggregation. In all of them, the native structure is stabilized by a disulfide bridge

This perspective aims to identify the relationships between the structural and dynamic properties of chromosomes and the fundamental properties of soft-matter systems. Chromatin is condensed into metaphase chromosomes during mitosis. The resulting structures are elongated cylinders having micrometer-scale dimensions. Our previous studies, using transmission electron microscopy, atomic force microscopy

It is established that for CRISPR-Cas9 applications guide RNAs with 17–20bp long spacer sequences are optimal for accurate target binding and cleavage. In this work we perform cell-free CRISPRa (CRISPR activation) and CRISPRi (CRISPR inhibition) experiments to demonstrate the existence of a complex dependence of CRISPR-Cas9 binding as a function of the spacer length and complementarity. Our results

Bacterial biofilms are communities of bacteria that exist as aggregates that can adhere to surfaces or be free-standing. This complex, social mode of cellular organization is fundamental to the physiology of microbes and often exhibits surprising behavior. Bacterial biofilms are more than the sum of their parts: single-cell behavior has a complex relation to collective community behavior, in a manner

A population can be immune to epidemics even if not all of its individual members are immune to the disease, so long as sufficiently many are immune—this is the traditional notion of herd immunity. In the smartphone era a population can be immune to epidemics even if not a single one of its members is immune to the disease—a notion we call ‘digital herd immunity’, which is similarly an emergent characteristic

A common signature of cell adaptation to stress is the improved resistance upon priming by prior stress exposure. In the context of hyperthermia, priming or preconditioning with sublethal heat shock can be a useful tool to confer thermotolerance and competitive advantage to cells. In the present study, we develop a data-driven modeling framework that is simple and generic enough to capture a broad

While the mathematical laws of uncontrolled epidemic spreading are well known, the statistical physics of coronavirus epidemics with containment measures is currently lacking. The modelling of available data of the first wave of the Covid-19 pandemic in 2020 over 230 days, in different countries representative of different containment policies is relevant to quantify the efficiency of these policies

Cells respond heterogeneously to molecular and environmental perturbations. Phenotypic heterogeneity, wherein multiple phenotypes coexist in the same conditions, presents challenges when interpreting the observed heterogeneity. Advances in live cell microscopy allow researchers to acquire an unprecedented amount of live cell image data at high spatiotemporal resolutions. Phenotyping cellular dynamics

It is conceivable that an RNA virus could use a polysome, that is, a string of ribosomes covering the RNA strand, to protect the genetic material from degradation inside a host cell. This paper discusses how such a virus might operate, and how its presence might be detected by ribosome profiling. There are two possible forms for such a polysomally protected virus, depending upon whether just the forward

Recent experiments and thermodynamic arguments suggest that mitochondrial temperatures are higher than those of the cytoplasm. A “hot mitochondrion” calls for a closer examination of the energy balance that endows it with these claimed elevated temperatures. As a first step in this effort, we present here a semi-quantitative bookkeeping whereby, in one stroke, a formula is proposed that yields the

Many bacteria communicate using diffusible pheromone signals known as autoinducers. When the autoinducer concentration reaches a threshold, which requires a minimum population density or ‘quorum’, the bacteria activate specific gene regulatory pathways. Simple diffusion of autoinducer can activate quorum-dependent pathways in cells that are located at substantial distances from the secreting source

Cell migration, which is regulated by intracellular signaling pathways (ICSP) and extracellular matrix (ECM), plays an indispensable role in many physiological and pathological process such as normal tissue development and cancer metastasis. However, there is a lack of rigorous and quantitative tools for analyzing the time-varying characteristics of cell migration in heterogeneous microenvironment

During epithelial morphogenesis, force generation at the cellular level not only causes cell deformation, but may also produce coordinated cell movement and rearrangement on the tissue level. In this paper, we use a novel three-dimensional vertex model to explore the roles of cellular forces during the formation of the salivary gland in the Drosophila embryo. Representing the placode as an epithelial

Chromatin loops inside the nucleus can be stable for a very long time, which remains poorly understood. Such a time is crucial for chromatin organization maintenance and stability. We explore here several physical scenarios, where loop maintenance is due to diffusing cross-linkers (cohesin stabilized by two CTCF molecules) that can bind and unbind at the base of chromatin loops. Using a Markov chain

In this paper, we demonstrate the application of MATLAB to develop a pandemic prediction system based on Simulink. The susceptible-exposed-asymptomatic but infectious-symptomatic and infectious (severe infected population + mild infected population)-recovered-deceased (SEAI(I 1 + I 2)RD) physical model for unsupervised learning and two types of supervised learning, namely, fuzzy proportional–integral–derivative

Cells and microorganisms adopt various strategies to migrate in response to different environmental stimuli. To date, many modeling research has focused on the crawling-based Dictyostelium discoideum (Dd) cells migration induced by chemotaxis, yet recent experimental results reveal that even without adhesion or contact to a substrate, Dd cells can still swim to follow chemoattractant signals. In this

The number of motors carrying cargos in biological cells is not well-defined, instead varying from cargo to cargo about a statistical mean. Predictive understanding of motility in cells therefore requires quantitative insights into mixed ensembles of cargos. Toward this goal, here we employed Monte Carlo simulations to investigate statistical ensembles of cargos carried by a Poisson-distributed number

Biological organisms experience constantly changing environments, from sudden changes in physiology brought about by feeding, to the regular rising and setting of the Sun, to ecological changes over evolutionary timescales. Living organisms have evolved to thrive in this changing world but the general principles by which organisms shape and are shaped by time varying environments remain elusive. Our

In a previous work (Huber etal. 2020 Phys. Biol. 17 065010), we discussed virus transmission dynamics modified by a uniform clustering of contacts in the population: close contacts within households and more distant contacts between households. In this paper, we discuss testing and tracing in such a stratified population. We propose a minimal tracing strategy consisting of random testing of the entire

The detachment of cells from the boundary of an epithelial tissue and the subsequent invasion of these cells into surrounding tissues is important for cancer development and wound healing, and is strongly associated with the epithelial–mesenchymal transition (EMT). Chemical signals, such as TGF-β, produced by surrounding tissue can be uptaken by cells and induce EMT. In this work, we present a novel

By end of October 2020, the COVID-19 pandemic has taken a tragic toll of 1150 000 lives and this number is expected to increase. Despite the pandemic is raging in most parts of the world, in a few countries COVID-19 epidemics subsided due to successful implementations of intervention measures. A unifying perspective of the beginnings, middle stages, and endings of such completed COVID-19 epidemics

Decoding the dynamics of cellular decision-making and cell differentiation is a central question in cell and developmental biology. A common network motif involved in many cell-fate decisions is a mutually inhibitory feedback loop between two self-activating ‘master regulators’ A and B, also called as toggle switch. Typically, it can allow for three stable states—(high A, low B), (low A, high B) and

During epithelial morphogenesis, force generation at the cellular level not only causes cell deformation, but may also produce coordinated cell movement and rearrangement on the tissue level. In this paper, we use a novel three-dimensional vertex model to explore the roles of cellular forces during the formation of the salivary gland in the Drosophila embryo. Representing the placode as an epithelial

In this paper, we demonstrate the application of MATLAB to develop a pandemic prediction system based on Simulink. The Susceptible-Exposed-Asymptomatic but infectious-symptomatic and Infectious (Severe Infected Population + Mild Infected Population)-Recovered-Deceased (SEAI(I1+I2)RD) physical model for unsupervised learning and two types of supervised learning, namely, fuzzy proportional-integral-derivative

Chromatin loops inside the nucleus can be stable for a very long time, which remains poorly understood. Such a time is crucial for chromatin organization maintenance and stability. We explore here several physical scenarios, where loop maintenance is due to diffusing cross-linkers (cohesin stabilized by two CTCF molecules) that can bind and unbind at the base of chromatin loops. Using a Markov chain

Recent experiments and thermodynamic arguments suggest that mitochondrial temperatures are higher than those of the cytoplasm. A "hot mitochondrion" calls for a closer examination of the energy balance that endows it with these claimed elevated temperatures. As a first step in this effort, we present here a semi-quantitative bookkeeping whereby, in one stroke, a formula is proposed that yields the

Cells and microorganisms adopt various strategies to migrate in response to different environmental stimuli. To date, many modeling research has focused on the crawling-based Dictyostelium discoideum (Dd) cells migration induced by chemotaixs, yet recent experimental results reveal that even without adhesion or contact to a substrate, Dd cells can still swim to follow chemoattractant signals. In this

The way in which interactions between mechanics and biochemistry lead to the emergence of complex cell and tissue organization is an old question that has recently attracted renewed interest from biologists, physicists, mathematicians and computer scientists. Rapid advances in optical physics, microscopy and computational image analysis have greatly enhanced our ability to observe and quantify spatiotemporal

It is conceivable that an RNA virus could use a polysome, that is, a string of ribosomes covering the RNA strand, to protect the genetic material from degradation inside a host cell. This paper discusses how such a virus might operate, and how its presence might be detected by ribosome profiling. There are two possible forms for such a polysomally protected virus, depending upon whether just the forward

A population can be immune to epidemics even if not all of its individual members are immune to the disease, so long as sufficiently many are immune-this is the traditional notion of herd immunity. In the smartphone era a population can be immune to epidemicseven if not a single one of its members is immune to the disease-a notion we call "digital herd immunity'', which is similarly an emergent characteristic

By end of October 2020, the COVID-19 pandemic has taken a tragic toll of 1.150.000 lives and this number is expected to increase. Despite the pandemic is raging in most parts of the world, in a few countries COVID-19 epidemics subsided due to successful implementations of intervention measures. A unifying perspective of the beginnings, middle stages, and endings of such completed COVID-19 epidemics

Decoding the dynamics of cellular decision-making and cell differentiation is a central question in cell and developmental biology. A common network motif involved in many cell-fate decisions is a mutually inhibitory feedback loop between two self-activating 'master regulators' A and B, also called as toggle switch. Typically, it can allow for three stable states - (high A, low B), (low A, high B)

When the hydration shell of a protein is filled with at least 0.6 gram of water per gram of protein, a significant anti-correlation between the vibrational free energy and the potential energy of energy-minimized conformers is observed. This means that low potential energy, well-hydrated, protein conformers tend to be more rigid than high-energy ones. On the other hand, in the case of CASP target 624

We consider a generic biological process described by a dynamical system, subject to an input signal with a high-frequency periodic component. The rapid oscillations of the input signal induce inherently multiscale dynamics, motivating order-reduction techniques. It is intuitive that the system behaviour is well approximated by its response to the averaged input signal. However, changes to the high-frequency

Cells use protein-based mechanosensors to measure the physical properties of their surroundings. Synthetic tension sensors made of proteins, DNA, and other molecular building blocks have recently emerged as tools to visualize and perturb the mechanics of these mechanosensors. While almost all synthetic tension sensors are designed to exhibit orientation-independent force responses, recent work has

Three-dimensional (3D) multi-cellular aggregates hold important applications in tissue engineering and in vitro biological modeling. Probing the intrinsic forces generated during the aggregation process, could open up new possibilities in advancing the discovery of tissue mechanics-based biomarkers. We use individually suspended, and tethered gelatin hydrogel microfibers to guide multicellular aggregation

Tumors are highly heterogeneous, consisting of cell populations with both transcriptional and genetic diversity. These diverse cell populations are spatially organized within a tumor, creating a distinct tumor microenvironment. A new technology called spatial transcriptomics can measure spatial patterns of gene expression within a tissue by sequencing RNA transcripts from a grid of spots, each containing

An important feature of the branch morphogenesis during kidney development is the termination of the tips on the outer surface of a kidney. This feature requires the avoidance of the intersection between the tips and existing ducts inside the kidney. Here, we started from a continuous model and implemented the coarse grained rules into a fast and discrete simulations. The ligand–receptor-based Turing

Melanogenesis is a highly regulated process through which the pigment melanin is produced in skin cells. Irregularities in the molecular events that govern the process of skin pigmentation can cause disorders like vitiligo. In order to understand the biology of disease progression, it is important to have an in depth understanding of intracellular events. Mathematical models provide an integrated view

The improved in vitro regulation of human embryonic stem cell (hESC) pluripotency and differentiation trajectories is required for their promising clinical applications. The temporal and spatial quantification of the molecular interactions controlling pluripotency is also necessary for the development of successful mathematical and computational models. Here we use time-lapse experimental data of OCT4-mCherry

Quick responses to fast changes in the environment are crucial in animal behaviour and survival, for example to seize prey, escape predators, or negotiate obstacles. Here, we study the ‘simple response time’ that is the time elapsed between receptor stimulation and motor activation as typically shown in escape responses, for mobile organisms of various taxa ranging from bacteria to large vertebrates

After the spread of COVID-19 out of China, the evolution of the pandemic has shown remarkable similarities and differences between countries around the world. Eventually, such characteristics are also observed between different regions of the same country. Herewith, we introduce a general method that allows us to compare the evolution of the pandemic in different localities inside a large territorial

In many biological systems, chemical reactions or changes in a physical state are assumed to occur instantaneously. For describing the dynamics of those systems, Markov models that require exponentially distributed inter-event times have been used widely. However, some biophysical processes such as gene transcription and translation are known to have a significant gap between the initiation and the

Using as a template the crystal structure of the SARS-CoV-2 main protease, we developed a pharmacophore model of functional centers of the protease inhibitor-binding pocket. With this model, we conducted data mining of the conformational database of FDA-approved drugs. This search brought 64 compounds that can be potential inhibitors of the SARS-CoV-2 protease. The conformations of these compounds

Nanoscale structural alteration in the nuclei of cells with the progression of carcinogenesis is due to the rearrangements of the basic building blocks in the cell such as DNA, RNA, lipids, etc. Although epigenetic modifications underlie the development of cancer, exposure to carcinogenic chemicals such as alcohol also enhances the development of cancer. We report the effects of chronic alcoholism

Microfluidic-based fluorescent exclusion method allows to tackle the issue of neuronal growth from a volume perspective. Based on this technology, we studied the two main actin-rich structures accompanying the early stages of neuron development, i.e. growth cones, located at the tip of growing neuronal processes, and propagative actin waves. Our work reveals that growth cones tend to loose volume during

Cell fate decision-making events involve the interplay of many molecular processes, ranging from signal transduction to genetic regulation, as well as a set of molecular and physiological feedback loops. Each aspect offers a rich field of investigation in its own right, but to understand the whole process, even in simple terms, we need to consider them together. Here we attempt to characterise this

Microbial range expansion experiments provide insight into the complex link between dynamic structure, pattern formation and evolutionary dynamics of growing populations. In this work, we develop a theoretical model in order to investigate the interplay of growth statistics and mechanical interactions which are implemented as division driven pushing and swapping of cells. For the case of the competitive

The nucleus of eukaryotic cells harbors active and out of equilibrium environments conducive to diverse gene regulatory processes. On a molecular scale, gene regulatory processes take place within hierarchically compartmentalized sub-nuclear bodies. While the impact of nuclear structure on gene regulation is widely appreciated, it has remained much less clear whether and how gene regulation is impacting

In the intracellular environment, the intrinsic dynamics of microtubule filaments is often hindered by the presence of barriers of various kind, such as kinetochore complexes and cell cortex, which impact their polymerisation force and dynamical properties such as catastrophe frequency. We present a theoretical study of the effect of a forced barrier, also subjected to thermal noise, on the statistics

Efficient nucleotide import is critical to fuel the reverse DNA synthesis that takes place within the HIV-1 capsid. However, the mechanism by which the HIV-1 capsid imports nucleotides is presently unclear. In this work, we carry out a series of Brownian diffusion simulations to elucidate the nucleotide import process through the hexamer pores of the HIV-1 capsid. Our simulations reveal a significant

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease and represents the most common disease of this type, after Alzheimer’s dementia. It is characterized by motor and nonmotor features and by a long prodromal stage that lasts many years. Genetic research has shown that PD is a complex and multisystem disorder. To capture the molecular complexity of this disease we used a complex

The proper functions of tissues depend on the ability of cells to withstand stress and maintain shape. Central to this process is the cytoskeleton, comprised of three polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). IF proteins are among the most abundant cytoskeletal proteins in cells; yet they remain some of the least understood. Their structure and function deviate from