arXiv subjects

Andrea Parmeggiani

Publications and source records attributed to Andrea Parmeggiani.

13 recordsLinked to original sources

arXiv2026

A mathematical modelling of rheumatoid arthritis

We developed a mathematical model to describe the inflammatory dynamics during arthritis development and resolution, focusing on the interaction between three key immune cell populations within the joint tissue, namely neutrophils (N), sublining synovial tissue-resident macrophages (SL-TRM, T), and circulating monocytes that are recruited into the inflamed joint and differentiate into monocyte-derived macrophages (MoMac, M). An inflammatory signal (S), representing the response to an external arthritogenic stimulus, drives the recruitment and activation of neutrophils and MoMac, while SL-TRM exert a regulatory and protective role. We propose a minimal ordinary differential equation model of acute inflammatory response into a joint that couples an inflammatory signal S to the three cell populations (N, T, M) and incorporates recruitment, stimulation, nonlinear self-limitation and mutual regulation. We show that the equilibrium structure depends on three adimensional parameters A, B, C and derive a cubic equation characterizing nontrivial steady states. We perform an analytical study of equilibria and their stability, and identify a bifurcation at A = 1 separating a disease-free regime from a sustained inflammatory state. Numerical simulations illustrate typical transient dynamics under various scenarios and show the ability of the model to capture the transition from acute to chronic inflammation, as well as the resolution of inflammation under certain conditions. In conclusion, our model provides a framework to explore mechanisms underlying acute versus sustained joint inflammation and offers a basis for parameter estimation from experimental data, as well as future extensions toward evaluation of therapeutic strategies.

math.DS↗

arXiv2026

Enhancer-promoter proximity predicts transcriptional competence but not transcriptional output in the Drosophila brain

How 3D genome architecture contributes to transcriptional specificity across neuronal cell types remains unclear. Here, we used multiplexed chromatin tracing to map chromatin architecture and cell identity at single-cell resolution in the adult Drosophila brain. We found that enhancer-promoter (E-P) proximity was increased in transcriptionally active compared with inactive neurons. Analysis of single traces revealed the existence of distinct proximal and distal E-P states, with active neurons enriched in the proximal state. However, this relationship broke down across active neuronal subtypes, where neither E-P proximity nor chromatin accessibility predicted transcriptional output. Thus, 3D genome organization distinguishes transcriptionally competent from inactive neuronal states without quantitatively specifying transcriptional output. Our findings support a model in which E-P proximity establishes a permissive structural state, while additional cell-type-specific regulatory mechanisms tune transcriptional output.

q-bio.GN↗

arXiv2024

Signature of (anti)cooperativity in the stochastic fluctuations of small systems: application to the bacterial flagellar motor

The cooperative binding of molecular agents onto a substrate is pervasive in living systems. To study whether a system shows cooperativity, one can rely on a fluctuation analysis of quantities such as the number of substrate-bound units and the residence time in an occupancy state. Since the relative standard deviation from the statistical mean monotonically decreases with the number of binding sites, these techniques are only suitable for small enough systems, such as those implicated in stochastic processes inside cells. Here, we present a general-purpose grand canonical Hamiltonian description of a small one-dimensional (1D) lattice gas with either nearest-neighbor or long-range interactions as prototypical examples of cooperativity-influenced adsorption processes. First, we elucidate how the strength and sign of the interaction potential between neighboring bound particles on the lattice determine the intensity of the fluctuations of the mean occupancy. We then employ this relationship to compare the theoretical predictions of our model to data from single molecule experiments on bacterial flagellar motors (BFM) of E. coli. In this way, we find evidence that cooperativity controls the mechano-sensitive dynamical assembly of the torque-generating units, the so-called stator units, onto the BFM. Furthermore, in an attempt to quantify fluctuations and the adaptability of the BFM, we estimate the stator-stator interaction potential. Finally, we conclude that the system resides in a sweet spot of the parameter space (phase diagram) suitable for a smoothly adaptive system while minimizing fluctuations.

physics.bio-ph↗

arXiv2022

Physical modeling of ribosomes along messenger RNA: estimating kinetic parameters from ribosome profiling experiments using a ballistic model

Gene expression consists in the synthesis of proteins from the information encoded on DNA. One of the two main steps of gene expression is the translation of messenger RNA (mRNA) into polypeptide sequences of amino acids. Here, by taking into account mRNA degradation, we model the motion of ribosomes along mRNA with a ballistic model where particles advance along a filament without excluded volume interactions. Unidirectional models of transport have previously been used to fit the average density of ribosomes obtained by the experimental ribo-sequencing (Ribo-seq) technique. In this case an inverse fit gives access to the kinetic rates: the position-dependent speeds and the entry rate of ribosomes onto mRNA. The degradation rate is not, however, accounted for and experimental data from different experiments are needed to have enough parameters for the fit. Here, we propose an entirely novel experimental setup and theoretical framework consisting in splitting the mRNAs into categories depending on the number of ribosomes from one to four. We solve analytically the ballistic model for a fixed number of ribosomes per mRNA, study the different regimes of degradation, and propose a criteria for the quality of the inverse fit. The proposed method provides a high sensitivity to the mRNA degradation rate. The additional equations coming from using the monosome (single ribosome) and polysome (arbitrary number) ribo-seq profiles enable us to determine all the kinetic rates in terms of the experimentally accessible mRNA degradation rate.

physics.bio-ph↗

arXiv2022

Modelling the effect of ribosome mobility on the rate of protein synthesis

Translation is one of the main steps in the synthesis of proteins. It consists of ribosomes that translate sequences of nucleotides encoded on mRNA into polypeptide sequences of amino acids. Ribosomes bound to mRNA move unidirectionally, while unbound ribosomes diffuse in the cytoplasm. It has been hypothesized that finite diffusion of ribosomes plays an important role in ribosome recycling and that mRNA circularization enhances the efficiency of translation. In order to estimate the effect of cytoplasmic diffusion on the rate of translation, we consider a Totally Asymmetric Simple Exclusion Process (TASEP) coupled to a finite diffusive reservoir, which we call the Ribosome Transport model with Diffusion (RTD). In this model, we derive an analytical expression for the rate of protein synthesis as a function of the diffusion constant of ribosomes, which is corroborated with results from continuous-time Monte Carlo simulations. Using a wide range of biological relevant parameters, we conclude that diffusion in biological cells is fast enough so that it does not play a role in controlling the rate of translation initiation.

q-bio.SC↗

arXiv2020

Stochastic modelling of collective motor protein transport through a crossing of microtubules

The cytoskeleton in eukaryotic cells plays several crucial roles. In terms of intracellular transport, motor proteins use the cytoskeletal filaments as a backbone along which they can actively transport biological cargos such as vesicles carrying biochemical reactants. Crossings between such filaments constitute a key element, as they may serve to alter the destination of such payload. Although motor proteins are known to display a rich behaviour at such crossings, the latter have so far only been modelled as simple branching points. Here we explore a model for a crossing between two microtubules which retains the individual tracks consisting of protofilaments, and we construct a schematic representation of the transport paths. We study collective transport exemplified by the Totally Asymmetric Simple Exclusion Process (TASEP), and provide a full analysis of the transport features and the associated phase diagram, by a generic mean-field approach which we confirm through particle-based stochastic simulations. In particular we show that transport through such a compound crossing cannot be approximated from a coarse-grained structure with a simple branching point. Instead, it gives rise to entirely new and counterintuitive features: the fundamental current-density relation for traffic flow is no longer a single-valued function, and it furthermore differs according to whether it is observed upstream or downstream from the crossing. We argue that these novel features may be directly relevant for interpreting experimental measurements.

physics.bio-ph↗

arXiv2020

Modeling supercoiled DNA interacting with an anchored cluster of proteins: towards a quantitative estimation of chromosomal DNA supercoiling

We investigate the measurement of DNA supercoiling density ($σ$) along chromosomes using interaction frequencies between DNA and DNA-anchored clusters of proteins. Specifically, we show how the physics of DNA supercoiling leads, in bacteria, to the quantitative modeling of binding properties of ParB proteins around their centromere-like site, {\it parS}. Using this framework, we provide an upper bound for $σ$ in the {\it Escherichia coli} chromosome, consistent with plasmid values, and offer a proof of concept for a high accuracy measurement. To reach these conclusions, we revisit the problem of the formation of ParB clusters. We predict, in particular, that they result from a non-equilibrium, stationary balance between an influx of produced proteins and an outflux of excess proteins, i.e., they behave like liquid-like protein condensates with unconventional ``leaky'' boundaries.

physics.bio-ph↗

arXiv2017

Looping and Clustering model for the organization of protein-DNA complexes on the bacterial genome

The bacterial genome is organized in a structure called the nucleoid by a variety of associated proteins. These proteins can form complexes on DNA that play a central role in various biological processes, including chromosome segregation. A prominent example is the large ParB-DNA complex, which forms an essential component of the segregation machinery in many bacteria. ChIP-Seq experiments show that ParB proteins localize around centromere-like parS sites on the DNA to which ParB binds specifically, and spreads from there over large sections of the chromosome. Recent theoretical and experimental studies suggest that DNA-bound ParB proteins can interact with each other to condense into a coherent 3D complex on the DNA. However, the structural organization of this protein-DNA complex remains unclear, and a predictive quantitative theory for the distribution of ParB proteins on DNA is lacking. Here, we propose the Looping and Clustering (LC) model, which employs a statistical physics approach to describe protein-DNA complexes. The LC model accounts for the extrusion of DNA loops from a cluster of interacting DNA-bound proteins. Conceptually, the structure of the protein-DNA complex is determined by a competition between attractive protein interactions and the configurational and loop entropy of this protein-DNA cluster. Indeed, we show that the protein interaction strength determines the "tightness" of the loopy protein-DNA complex. With this approach we consider the genomic organization of such a protein-DNA cluster around a single high-affinity binding site. Thus, our model provides a theoretical framework to quantitatively compute the binding profiles of ParB-like proteins around a cognate (parS) binding site.

physics.bio-ph↗

arXiv2017

Surfing on protein waves: proteophoresis as a mechanism for bacterial genome partitioning

Efficient bacterial chromosome segregation typically requires the coordinated action of a three-components, fueled by adenosine triphosphate machinery called the partition complex. We present a phenomenological model accounting for the dynamic activity of this system. The model is obtained by coupling simple linear reaction-diffusion equations with a proteophoresis, or "volumetric" chemophoresis, force field. This minimal description, in the sense of Occam's Razor principle, captures most known experimental observations: dynamic oscillations of complex components, complex separation and subsequent symmetrical positioning. The predictions of our model are in phenomenological agreement with and provide substantial insights into recent experiments. From a non-linear physics view point, this system explores the active separation of matter at micrometric scales with a dynamical instability between static positioning and travelling wave regimes.

q-bio.SC↗

arXiv2013

Transport on a Lattice with Dynamical Defects

Many transport processes in nature take place on substrates, often considered as unidimensional lanes. These unidimensional substrates are typically non-static: affected by a fluctuating environment, they can undergo conformational changes. This is particularly true in biological cells, where the state of the substrate is often coupled to the active motion of macromolecular complexes, such as motor proteins on microtubules or ribosomes on mRNAs, causing new interesting phenomena. Inspired by biological processes such as protein synthesis by ribosomes and motor protein transport, we introduce the concept of localized dynamical sites coupled to a driven lattice gas dynamics. We investigate the phenomenology of transport in the presence of dynamical defects and find a novel regime characterized by an intermittent current and subject to severe finite-size effects. Our results demonstrate the impact of the regulatory role of the dynamical defects in transport, not only in biology but also in more general contexts.

cond-mat.stat-mech↗

arXiv2005

Renewal processes and fluctuation analysis of molecular motor stepping

We model the dynamics of a processive or rotary molecular motor using a renewal processes, in line with the work initiated by Svoboda, Mitra and Block. We apply a functional technique to compute different types of multiple-time correlation functions of the renewal process, which have applications to bead-assay experiments performed both with processive molecular motors, such as myosin V and kinesin, and rotary motors, such as F1-ATPase.

cond-mat.stat-mech↗

arXiv2003

Internal Motility in Stiffening Actin-Myosin Networks

We present a study on filamentous actin solutions containing heavy meromyosin subfragments of myosin II motor molecules. We focus on the viscoelastic phase behavior and internal dynamics of such networks during ATP depletion. Upon simultaneously using micro-rheology and fluorescence microscopy as complementary experimental tools, we find a sol-gel transition accompanied by a sudden onset of directed filament motion. We interpret the sol-gel transition in terms of myosin II enzymology, and suggest a "zipping" mechanism to explain the filament motion in the vicinity of the sol-gel transition.

physics.bio-ph↗

arXiv1999

Energy Transduction of Isothermal Ratchets: Generic Aspects and Specific Examples Close to and Far from Equilibrium

We study the energetics of isothermal ratchets which are driven by a chemical reaction between two states and operate in contact with a single heat bath of constant temperature. We discuss generic aspects of energy transduction such as Onsager relations in the linear response regime as well as the efficiency and dissipation close to and far from equilibrium. In the linear response regime where the system operates reversibly the efficiency is in general nonzero. Studying the properties for specific examples of energy landscapes and transitions, we observe in the linear response regime that the efficiency can have a maximum as a function of temperature. Far from equilibrium in the fully irreversible regime, we find a maximum of the efficiency with values larger than in the linear regime for an optimal choice of the chemical driving force. We show that corresponding efficiencies can be of the order of 50%. A simple analytic argument allows us to estimate the efficiency in this irreversible regime for small external forces.

cond-mat.stat-mech↗