Journal of Theoretical Biology最新文献

{"title":"Pulmonary epithelial wound healing and the immune system. Mathematical modeling and bifurcation analysis of a bistable system","authors":"Clara R. Lotter,&nbsp;Jonathan A. Sherratt","doi":"10.1016/j.jtbi.2024.111968","DOIUrl":"10.1016/j.jtbi.2024.111968","url":null,"abstract":"<div><div>Respiratory diseases such as asthma, acute respiratory distress syndrome (ARDS), influenza or COVID-19 often directly target the epithelium. Elevated immune levels and a ‘cytokine storm’ are directly associated with defective healing dynamics of lung diseases such as COVID-19 or ARDS. The infected cells leave wounded regions in the epithelium which must be healed for the lung to return to a healthy state and carry out its main function of gas-exchange. Due to the complexity of the various interactions between cells of the lung epithelium and surrounding tissue, it is necessary to develop models that can complement experiments to fully understand the healing dynamics. In this mathematical study we model the mechanism of epithelial regeneration. We assume that healing is exclusively driven by progenitor cell proliferation, induced by a chemical activator such as epithelial growth factor (EGF) and cytokines such as interleukin-22 (IL22). Contrary to previous studies of wound healing, we consider the immune system, specifically the T effector cells TH1, TH17, TH22 and Treg to strongly contribute to the healing process, by producing IL22 or regulating the immune response. We therefore obtain a coupled system of two ordinary differential equations for the epithelial and immune cell densities and two functions for the levels of chemicals that either induce epithelial proliferation or recruit immune cells. These functions link the two cell equations. We find that to allow the epithelium to regenerate to a healthy state, the immune system must not exceed a threshold value at the onset of the healing phase. This immune threshold is supported experimentally but was not explicitly built into our equations. Our assumptions are therefore sufficient to reproduce experimental results concerning the ratio TH17/Treg cells as a threshold to predict higher mortality rates in patients. This immune threshold can be controlled by parameters of the model, specifically the base-level growth factor concentration. This conclusion is based on a mathematical bifurcation analysis and linearization of the model equations. Our results suggest treatment of severe cases of lung injury by reducing or suppressing the immune response, in an individual patient, assessed by their disease parameters such as course of lung injury and immune response levels.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"596 ","pages":"Article 111968"},"PeriodicalIF":1.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PULSAR Effect: Revealing potential synergies in combined radiation therapy and immunotherapy via differential equations","authors":"Samiha Rouf ,&nbsp;Casey Moore ,&nbsp;Debabrata Saha ,&nbsp;Dan Nguyen ,&nbsp;MaryLena Bleile ,&nbsp;Robert Timmerman ,&nbsp;Hao Peng ,&nbsp;Steve Jiang","doi":"10.1016/j.jtbi.2024.111974","DOIUrl":"10.1016/j.jtbi.2024.111974","url":null,"abstract":"<div><div>PULSAR (personalized ultrafractionated stereotactic adaptive radiotherapy) is a form of radiotherapy method where a patient is given a large dose or “pulse” of radiation a couple of weeks apart rather than daily small doses. The tumor response is then monitored to determine when the subsequent pulse should be given. Pre-clinical trials have shown better tumor response in mice that received immunotherapy along with pulses spaced 10 days apart. However, this was not the case when the pulses were 1 or 4 days apart. Therefore, a synergistic effect between immunotherapy and PULSAR is observed when the pulses are spaced out by a certain number of days. In our study, we aimed to develop a mathematical model that can capture the synergistic effect by considering a time-dependent weight function that takes into account the spacing between pulses. We determined feasible parameters by fitting murine tumor volume data of six treatment groups via simulated annealing algorithm. Applying these parameters to the model we simulated 4000 trials with varying sequencing of pulses. These simulations indicated that if pulses were spaced apart by at least 9 days the tumor volume was about 200 <span><math><mrow><mi>m</mi><msup><mrow><mi>m</mi></mrow><mn>3</mn></msup></mrow></math></span> to 250 <span><math><mrow><mi>m</mi><msup><mrow><mi>m</mi></mrow><mn>3</mn></msup></mrow></math></span> smaller when treated with PULSAR combined with immunotherapy. We successfully demonstrate that our model is simple to implement and can generate tumor volume data that is consistent with the pre-clinical trial data. Our model has the potential to aid in the development of clinical trials of PULSAR therapy.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"596 ","pages":"Article 111974"},"PeriodicalIF":1.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A theoretical model for focal adhesion and cytoskeleton formation in non-motile cells","authors":"Gordon R. McNicol ,&nbsp;Matthew J. Dalby ,&nbsp;Peter S. Stewart","doi":"10.1016/j.jtbi.2024.111965","DOIUrl":"10.1016/j.jtbi.2024.111965","url":null,"abstract":"<div><div>To function and survive cells need to be able to sense and respond to their local environment through mechanotransduction. Crucially, mechanical and biochemical perturbations initiate cell signalling cascades, which can induce responses such as growth, apoptosis, proliferation and differentiation. At the heart of this process are actomyosin stress fibres (SFs), which form part of the cell cytoskeleton, and focal adhesions (FAs), which bind this cytoskeleton to the extra-cellular matrix (ECM). The formation and maturation of these structures (connected by a positive feedback loop) is pivotal in non-motile cells, where SFs are generally of ventral type, interconnecting FAs and producing isometric tension. In this study we formulate a one-dimensional bio-chemo-mechanical continuum model to describe the coupled formation and maturation of ventral SFs and FAs. We use a set of reaction–diffusion–advection equations to describe three sets of biochemical events: the polymerisation of actin and subsequent bundling into activated SFs; the formation and maturation of cell–substrate adhesions; and the activation of signalling proteins in response to FA and SF formation. The evolution of these key proteins is coupled to a Kelvin–Voigt viscoelastic description of the cell cytoplasm and the ECM. We employ this model to understand how cells respond to external and intracellular cues <em>in vitro</em> and are able to reproduce experimentally observed phenomena including non-uniform cell striation and cells forming weaker SFs and FAs on softer substrates.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"596 ","pages":"Article 111965"},"PeriodicalIF":1.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulating irregular symmetry breaking in gut cross sections using a novel energy-optimization approach in growth-elasticity","authors":"Min Wu","doi":"10.1016/j.jtbi.2024.111971","DOIUrl":"10.1016/j.jtbi.2024.111971","url":null,"abstract":"<div><div>Growth-elasticity (also known as morphoelasticity) is a powerful model framework for understanding complex shape development in soft biological tissues. At each instant, by mapping how continuum building blocks have grown geometrically and how they respond elastically to the push-and-pull from their neighbors, the shape of the growing structure is determined from a state of mechanical equilibrium. As mechanical loads continue to be added to the system through growth, many interesting shapes, such as smooth wavy wrinkles, sharp creases, and deep folds, can form on the tissue surface from a relatively flatter geometry.</div><div>Previous numerical simulations of growth-elasticity have reproduced many interesting shapes resembling those observed in reality, such as the foldings on mammalian brains and guts. In the case of mammalian guts, it has been shown that wavy wrinkles, deep folds, and sharp creases on the interior organ surface can be simulated even under a simple assumption of isotropic uniform growth in the interior layer of the organ. Interestingly, the simulated patterns are all regular along the tube’s circumference, with either all smooth or all sharp indentations, whereas some undulation patterns in reality exhibit irregular patterns and a mixture of sharp creases and smooth indentations along the circumference. Can we simulate irregular indentation patterns without further complicating the growth patterning?</div><div>In this paper, we have discovered abundant shape solutions with irregular indentation patterns by developing a Rayleigh–Ritz finite-element method (FEM). In contrast to previous Galerkin FEMs, which solve the weak formulation of the mechanical-equilibrium equations, the new method formulates an optimization problem for the discretized energy functional, whose critical points are equivalent to solutions obtained by solving the mechanical-equilibrium equations. This new method is more robust than previous methods. Specifically, it does not require the initial guess to be near a solution to achieve convergence, and it allows control over the direction of numerical iterates across the energy landscape. This approach enables the capture of more solutions that cannot be easily reached by previous methods. In addition to the previously found regular smooth and non-smooth configurations, we have identified a new transitional irregular smooth shape, new shapes with a mixture of smooth and non-smooth surface indentations, and a variety of irregular patterns with different numbers of creases. Our numerical results demonstrate that growth-elasticity modeling can match more shape patterns observed in reality than previously thought.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111971"},"PeriodicalIF":1.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resource budget model with Duffing oscillator for dynamics of synchronized biennial-bearing olives in the Levant","authors":"Eileen Joan Magero ,&nbsp;Koichi Unami ,&nbsp;Osama Mohawesh ,&nbsp;Marie Sato","doi":"10.1016/j.jtbi.2024.111973","DOIUrl":"10.1016/j.jtbi.2024.111973","url":null,"abstract":"<div><div>We develop and analyze a temporally continuous spatially lumped resource budget model to explain the dynamics of synchronized biennial-bearing olives in the Levant, specifically focusing on Syria, the region’s foremost olive-producing country. The model is a time-continuous counterpart of the celebrated resource budget model. It consists of a Duffing oscillator coupled with a dynamical model of pollination with an external force propelling olive growth by photosynthesis. The reference data are obtained from statistical databases of international organizations and our own observation systems in Jordan, a country neighboring Syria, providing a wealth of information to refine the model structure. An intensive review of Syria’s modern history involving significant shifts in agricultural policy and social stability leads to a conclusion that the model should comprehend the anomaly of olive yield interacting with socio-political factors as an autonomous behavior. The conventional mathematical methodology analyzes the model’s characteristics, such as solutions’ non-negativity, boundedness, and stability. The system is stable during pollination off-season but may become unstable and unbounded during pollination on-season, which is a property that the time-discrete resource budget model cannot reproduce. A significant finding is that coupling individual fruit trees by anemophily is not essential in synchronization, overturning earlier studies in the literature. The values of model parameters that best fit the historical data of olive yield in Syria result in bounded chaos. With alternative parameter values, the model could exhibit periodic oscillation, instability, or blowing up, as clearly shown in bifurcation diagrams.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111973"},"PeriodicalIF":1.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of 3D chaos game representation to quantify DNA sequence similarity with applications for hierarchical clustering","authors":"Stephanie Young ,&nbsp;Jérôme Gilles","doi":"10.1016/j.jtbi.2024.111972","DOIUrl":"10.1016/j.jtbi.2024.111972","url":null,"abstract":"<div><div>A 3D chaos game is shown to be a useful way for encoding DNA sequences. Since matching subsequences in DNA converge in space in 3D chaos game encoding, a DNA sequence’s 3D chaos game representation can be used to compare DNA sequences without prior alignment and without truncating or padding any of the sequences. Two proposed methods inspired by shape-similarity comparison techniques show that this form of encoding can perform as well as alignment-based techniques for building phylogenetic trees. The first method uses the volume overlap of intersecting spheres and the second uses shape signatures by summarizing the coordinates, oriented angles, and oriented distances of the 3D chaos game trajectory. The methods are tested using: (1) the first exon of the beta-globin gene for 11 species, (2) mitochondrial DNA from four groups of primates, and (3) a set of synthetic DNA sequences. Simulations show that the proposed methods produce distances that reflect the number of mutation events; additionally, on average, distances resulting from deletion mutations are comparable to those produced by substitution mutations.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"596 ","pages":"Article 111972"},"PeriodicalIF":1.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mathematical model of repressive response to collective action and protest waves","authors":"V. Volpert","doi":"10.1016/j.jtbi.2024.111970","DOIUrl":"10.1016/j.jtbi.2024.111970","url":null,"abstract":"<div><div>The intricate interplay between the state and society may foster opposition and prompt collective action as a mode of protest. When the state responds repressively to such collective action, it aims to undermine it escalating its costs. A mathematical model relating the repressive response to collective action, articulated through differential equations, facilitates a thorough analysis of their dynamic interaction. Modelling outcomes indicate that repressive regimes may exhibit sustained persistence, oscillatory patterns, or destabilization, potentially transitioning into alternative regimes. This modelling framework offers a means to discern the impact of diverse factors on the dynamics of repressive regimes and to provide modelling insight on the emergence of cycles of protest observed in different countries during certain periods of their history.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111970"},"PeriodicalIF":1.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JTB Editorial for Professor Denise Kirschner","authors":"Mark Chaplain (Journal of Theoretical Biology co-Chief Editor),&nbsp;Akira Sasaki (Journal of Theoretical Biology co-Chief Editor),&nbsp;Joshua Weitz (Journal of Theoretical Biology co-Chief Editor)","doi":"10.1016/j.jtbi.2024.111976","DOIUrl":"10.1016/j.jtbi.2024.111976","url":null,"abstract":"","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111976"},"PeriodicalIF":1.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probabilistic analysis of tumor growth inhibition models to Support trial design","authors":"Marcus Baaz ,&nbsp;Tim Cardilin ,&nbsp;Torbjörn Lundh ,&nbsp;Mats Jirstrand","doi":"10.1016/j.jtbi.2024.111969","DOIUrl":"10.1016/j.jtbi.2024.111969","url":null,"abstract":"<div><div>A large enough sample size of patients is required to statistically show that one treatment is better than another. However, too large a sample size is expensive and can also result in findings that are statistically significant, but not clinically relevant. How sample sizes should be chosen is a well-studied problem in classical statistics and analytical expressions can be derived from the appropriate test statistic. However, these expressions require information regarding the efficacy of the treatment, which may not be available, particularly for newly developed drugs. Tumor growth inhibition (TGI) models are frequently used to quantify the efficacy of newly developed anticancer drugs. In these models, the tumor growth dynamics are commonly described by a set of ordinary differential equations containing parameters that must be estimated using experimental data.</div><div>One widely used endpoint in clinical trials is the proportion of patients in different response categories determined using the Response Evaluation Criteria In Solid Tumors (RECIST) framework. From the TGI model, we derive analytical expressions for the probability of patient response to combination therapy. The probabilistic expressions are used together with classical statistics to derive a parametric model for the sample size required to achieve a certain significance level and test power when comparing two treatments.</div><div>Furthermore, the probabilistic expressions are used to generalize the Tumor Static Exposure concept to be more suitable for predicting clinical response. The derivatives of the probabilistic expressions are used to derive two additional expressions characterizing the exposure and its sensitivity. Finally, our results are illustrated using parameters obtained from calibrating the model to preclinical data.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111969"},"PeriodicalIF":1.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bulk-surface mechanobiochemical modelling approach for single cell migration in two-space dimensions","authors":"David Hernandez-Aristizabal ,&nbsp;Diego-Alexander Garzon-Alvarado ,&nbsp;Carlos-Alberto Duque-Daza ,&nbsp;Anotida Madzvamuse","doi":"10.1016/j.jtbi.2024.111966","DOIUrl":"10.1016/j.jtbi.2024.111966","url":null,"abstract":"<div><div>In this work, we present a mechanobiochemical model for two-dimensional cell migration which couples mechanical properties of the cell cytosol with biochemical processes taking place near or on the cell plasma membrane. The modelling approach is based on a recently developed mathematical formalism of evolving bulk-surface partial differential equations of reaction–diffusion type. We solve these equations using finite element methods within a moving-mesh framework derived from the weak formulation of the evolving bulk-surface PDEs. In the present work, the cell cytosol interior (bulk) dynamics are coupled to the cell membrane (surface) dynamics through non-homogeneous Dirichlet boundary conditions. The modelling approach exhibits both directed cell migration in response to chemical cues as well as spontaneous migration in the absence of such cues. As a by-product, the approach shows fundamental characteristics associated with single cell migration such as: (i) cytosolic and membrane polarisation, (ii) actin dependent protrusions, and (iii) continuous shape deformation of the cell during migration.</div><div>Cell migration is an ubiquitous process in life that is mainly triggered by the dynamics of the actin cytoskeleton and therefore is driven by both mechanical and biochemical processes. It is a multistep process essential for mammalian organisms and is closely linked to a vast diversity of processes; from embryonic development to cancer invasion. Experimental, theoretical and computational studies have been key to elucidate the mechanisms underlying cell migration. On one hand, rapid advances in experimental techniques allow for detailed experimental measurements of cell migration pathways, while, on the other, computational approaches allow for the modelling, analysis and understanding of such observations. The bulk-surface mechanobiochemical modelling approach presented in this work, set premises to study single cell migration through complex non-isotropic environments in two- and three-space dimensions.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"595 ","pages":"Article 111966"},"PeriodicalIF":1.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}