RESUMO
Plants are a paradigm for active shape control in response to stimuli. For instance, it is well known that a tilted plant will eventually straighten vertically, demonstrating the influence of both an external stimulus, gravity, and an internal stimulus, proprioception. These effects can be modulated when a potted plant is additionally rotated along the plant's axis, as in a rotating clinostat, leading to intricate shapes. We use a previously derived rod model to study the response of a growing plant and the joint effects of both stimuli at all rotation speeds. In the absence of rotation, we identify a universal planar shape towards which all shoots eventually converge. With rotation, we demonstrate the existence of a stable family of three-dimensional dynamic equilibria where the plant axis is fixed in space. Further, the effect of axial growth is to induce steady behaviors, such as solitary waves. Overall, this study offers insight into the complex out-of-equilibrium dynamics of a plant in three dimensions and further establishes that internal stimuli in active materials are key for robust shape control.
Assuntos
Modelos Biológicos , Rotação , Desenvolvimento Vegetal , Meio Ambiente , Brotos de Planta/crescimento & desenvolvimento , Plantas/metabolismoRESUMO
One of the key problems in active materials is the control of shape through actuation. A fascinating example of such control is the elephant trunk, a long, muscular, and extremely dexterous organ with multiple vital functions. The elephant trunk is an object of fascination for biologists, physicists, and children alike. Its versatility relies on the intricate interplay of multiple unique physical mechanisms and biological design principles. Here, we explore these principles using the theory of active filaments and build, theoretically, computationally, and experimentally, a minimal model that explains and accomplishes some of the spectacular features of the elephant trunk.
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Elefantes , Modelos Biológicos , Animais , Fenômenos BiomecânicosRESUMO
Dynamical systems on networks typically involve several dynamical processes evolving at different timescales. For instance, in Alzheimer's disease, the spread of toxic protein throughout the brain not only disrupts neuronal activity but is also influenced by neuronal activity itself, establishing a feedback loop between the fast neuronal activity and the slow protein spreading. Motivated by the case of Alzheimer's disease, we study the multiple-timescale dynamics of a heterodimer spreading process on an adaptive network of Kuramoto oscillators. Using a minimal two-node model, we establish that heterogeneous oscillatory activity facilitates toxic outbreaks and induces symmetry breaking in the spreading patterns. We then extend the model formulation to larger networks and perform numerical simulations of the slow-fast dynamics on common network motifs and on the brain connectome. The simulations corroborate the findings from the minimal model, underscoring the significance of multiple-timescale dynamics in the modeling of neurodegenerative diseases.
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Doença de Alzheimer , Encéfalo , Simulação por Computador , Conceitos Matemáticos , Modelos Neurológicos , Neurônios , Humanos , Doença de Alzheimer/fisiopatologia , Neurônios/fisiologia , Encéfalo/fisiopatologia , Conectoma , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/patologia , Rede Nervosa/fisiopatologia , Rede Nervosa/fisiologiaRESUMO
Correction to: Biomechanics and Modeling in Mechanobiology (2022) 21:89-118 https://doi.org/10.1007/s10237-021-01539-0.
RESUMO
Centrioles duplicate when a mother centriole gives birth to a daughter that grows from its side. Polo-like-kinase 4 (PLK4), the master regulator of centriole duplication, is recruited symmetrically around the mother centriole, but it then concentrates at a single focus that defines the daughter centriole assembly site. How PLK4 breaks symmetry is unclear. Here, we propose that phosphorylated and unphosphorylated species of PLK4 form the 2 components of a classical Turing reaction-diffusion system. These 2 components bind to/unbind from the surface of the mother centriole at different rates, allowing a slow-diffusing activator species of PLK4 to accumulate at a single site on the mother, while a fast-diffusing inhibitor species of PLK4 suppresses activator accumulation around the rest of the centriole. This "short-range activation/long-range inhibition," inherent to Turing systems, can drive PLK4 symmetry breaking on a either a continuous or compartmentalised Plk4-binding surface, with PLK4 overexpression producing multiple PLK4 foci and PLK4 kinase inhibition leading to a lack of symmetry-breaking and PLK4 accumulation-as observed experimentally.
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Proteínas de Ciclo Celular , Centríolos , Centríolos/metabolismo , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiologiaRESUMO
Carnivorous pitcher plants (Nepenthes) are a striking example of a natural pitfall trap. The trap's slippery rim, or peristome, plays a critical role in insect capture via an aquaplaning mechanism that is well documented. While the peristome has received significant research attention, the conspicuous variation in peristome geometry across the genus remains unexplored. We examined the mechanics of prey capture using Nepenthes pitcher plants with divergent peristome geometries. Inspired by living material, we developed a mathematical model that links the peristomes' three-dimensional geometries to the physics of prey capture under the laws of Newtonian mechanics. Linking form and function enables us to test hypotheses related to the function of features such as shape and ornamentation, orientation in a gravitational field, and the presence of "teeth," while analysis of the energetic costs and gains of a given geometry provides a means of inferring potential evolutionary pathways. In a separate modeling approach, we show how prey size may correlate with peristome dimensions for optimal capture. Our modeling framework provides a physical platform to understand how divergence in peristome morphology may have evolved in the genus Nepenthes in response to shifts in prey diversity, availability, and size.
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Evolução Biológica , Caryophyllales , Ligante de CD40 , Planta CarnívoraRESUMO
The separation of double-stranded peptide chains can occur in two ways: cooperatively or non-cooperatively. These two regimes can be driven either by chemical or thermal effects, or through non-local mechanical interactions. Here, we show explicitly that local mechanical interactions in biological systems may regulate the stability, the reversibility, and the cooperative/non-cooperative character of the debonding transition. We show that this transition is characterized by a single parameter depending on an internal length scale. Our theory describes a wide range of melting transitions found in biological systems such as protein secondary structures, microtubules and tau proteins, and DNA molecules. In these cases, the theory gives the critical force as a function of the chain length and its elastic properties. Our theoretical results provide quantitative predictions for known experimental effects that appear in different biological and biomedical fields.
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Microtúbulos , PeptídeosRESUMO
Tumour spheroids have been the focus of a variety of mathematical models, ranging from Greenspan's classical study of the 1970 s through to contemporary agent-based models. Of the many factors that regulate spheroid growth, mechanical effects are perhaps some of the least studied, both theoretically and experimentally, though experimental enquiry has established their significance to tumour growth dynamics. In this tutorial, we formulate a hierarchy of mathematical models of increasing complexity to explore the role of mechanics in spheroid growth, all the while seeking to retain desirable simplicity and analytical tractability. Beginning with the theory of morphoelasticity, which combines solid mechanics and growth, we successively refine our assumptions to develop a somewhat minimal model of mechanically regulated spheroid growth that is free from many unphysical and undesirable behaviours. In doing so, we will see how iterating upon simple models can provide rigorous guarantees of emergent behaviour, which are often precluded by existing, more complex modelling approaches. Perhaps surprisingly, we also demonstrate that the final model considered in this tutorial agrees favourably with classical experimental results, highlighting the potential for simple models to provide mechanistic insight whilst also serving as mathematical examples.
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Neoplasias , Esferoides Celulares , Humanos , Modelos Biológicos , Conceitos Matemáticos , Modelos TeóricosRESUMO
Alzheimer's disease is the most common cause of dementia and is linked to the spreading of pathological amyloid-ß and tau proteins throughout the brain. Recent studies have highlighted stark differences in how amyloid-ß and tau affect neurons at the cellular scale. On a larger scale, Alzheimer's patients are observed to undergo a period of early-stage neuronal hyperactivation followed by neurodegeneration and frequency slowing of neuronal oscillations. Herein, we model the spreading of both amyloid-ß and tau across a human connectome and investigate how the neuronal dynamics are affected by disease progression. By including the effects of both amyloid-ß and tau pathology, we find that our model explains AD-related frequency slowing, early-stage hyperactivation and late-stage hypoactivation. By testing different hypotheses, we show that hyperactivation and frequency slowing are not due to the topological interactions between different regions but are mostly the result of local neurotoxicity induced by amyloid-ß and tau protein.
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Doença de Alzheimer , Conectoma , Humanos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Neurônios , Encéfalo/metabolismoRESUMO
In March 2020 mathematics became a key part of the scientific advice to the UK government on the pandemic response to COVID-19. Mathematical and statistical modelling provided critical information on the spread of the virus and the potential impact of different interventions. The unprecedented scale of the challenge led the epidemiological modelling community in the UK to be pushed to its limits. At the same time, mathematical modellers across the country were keen to use their knowledge and skills to support the COVID-19 modelling effort. However, this sudden great interest in epidemiological modelling needed to be coordinated to provide much-needed support, and to limit the burden on epidemiological modellers already very stretched for time. In this paper we describe three initiatives set up in the UK in spring 2020 to coordinate the mathematical sciences research community in supporting mathematical modelling of COVID-19. Each initiative had different primary aims and worked to maximise synergies between the various projects. We reflect on the lessons learnt, highlighting the key roles of pre-existing research collaborations and focal centres of coordination in contributing to the success of these initiatives. We conclude with recommendations about important ways in which the scientific research community could be better prepared for future pandemics. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".
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COVID-19 , Pandemias , Humanos , Pandemias/prevenção & controle , COVID-19/epidemiologia , Aprendizagem , Matemática , Reino Unido/epidemiologiaRESUMO
We develop a mathematical model that builds on the surprising nonlinear mechanical response observed in recent experiments on nematic liquid crystal elastomers. Namely, under uniaxial tensile loads, the material, rather than thinning in the perpendicular directions, becomes thicker in one direction for a sufficiently large strain, while its volume remains unchanged. Motivated by this unusual large-strain auxetic behaviour, we model the material using an Ogden-type strain-energy function and calibrate its parameters to available datasets. We show that Ogden strain-energy functions are particularly suitable for modelling nematic elastomers because of their mathematical simplicity and their clear formulation in terms of the principal stretches, which have a direct kinematic interpretation. This article is part of the theme issue 'The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity'.
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Mitotic centrosomes are formed when centrioles start to recruit large amounts of pericentriolar material (PCM) around themselves in preparation for mitosis. This centrosome "maturation" requires the centrioles and also Polo/PLK1 protein kinase. The PCM comprises several hundred proteins and, in Drosophila, Polo cooperates with the conserved centrosome proteins Spd-2/CEP192 and Cnn/CDK5RAP2 to assemble a PCM scaffold around the mother centriole that then recruits other PCM client proteins. We show here that in Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during the assembly process-peaking, and then starting to decline, even as levels of the PCM scaffold continue to rise and plateau. Experiments and mathematical modelling indicate that a centriolar pulse of Polo activity, potentially generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), could explain these unexpected scaffold assembly dynamics. We propose that centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation, explaining why centrioles and Polo/PLK1 are normally essential for this process.
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Centríolos , Proteínas de Drosophila , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Centríolos/metabolismo , Centrossomo/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Mitose , Proteínas Serina-Treonina Quinases/genéticaRESUMO
The establishment of a functioning neuronal network is a crucial step in neural development. During this process, neurons extend neurites-axons and dendrites-to meet other neurons and interconnect. Therefore, these neurites need to migrate, grow, branch and find the correct path to their target by processing sensory cues from their environment. These processes rely on many coupled biophysical effects including elasticity, viscosity, growth, active forces, chemical signaling, adhesion and cellular transport. Mathematical models offer a direct way to test hypotheses and understand the underlying mechanisms responsible for neuron development. Here, we critically review the main models of neurite growth and morphogenesis from a mathematical viewpoint. We present different models for growth, guidance and morphogenesis, with a particular emphasis on mechanics and mechanisms, and on simple mathematical models that can be partially treated analytically.
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Axônios , Neuritos , Axônios/fisiologia , Modelos Teóricos , Morfogênese , Neuritos/fisiologia , NeurôniosRESUMO
Snails are model organisms for studying the genetic, molecular, and developmental bases of left-right asymmetry in Bilateria. However, the development of their typical helicospiral shell, present for the last 540 million years in environments as different as the abyss or our gardens, remains poorly understood. Conversely, ammonites typically have a bilaterally symmetric, planispiraly coiled shell, with only 1% of 3,000 genera displaying either a helicospiral or a meandering asymmetric shell. A comparative analysis suggests that the development of chiral shells in these mollusks is different and that, unlike snails, ammonites with asymmetric shells probably had a bilaterally symmetric body diagnostic of cephalopods. We propose a mathematical model for the growth of shells, taking into account the physical interaction during development between the soft mollusk body and its hard shell. Our model shows that a growth mismatch between the secreted shell tube and a bilaterally symmetric body in ammonites can generate mechanical forces that are balanced by a twist of the body, breaking shell symmetry. In gastropods, where a twist is intrinsic to the body, the same model predicts that helicospiral shells are the most likely shell forms. Our model explains a large diversity of forms and shows that, although molluscan shells are incrementally secreted at their opening, the path followed by the shell edge and the resulting form are partly governed by the mechanics of the body inside the shell, a perspective that explains many aspects of their development and evolution.
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Exoesqueleto/crescimento & desenvolvimento , Cefalópodes/crescimento & desenvolvimento , Cefalópodes/fisiologia , Caramujos/crescimento & desenvolvimento , Caramujos/fisiologia , Animais , Evolução Biológica , Fenômenos Mecânicos , Modelos Biológicos , Modelos Teóricos , Filogenia , Estresse MecânicoRESUMO
The timing and sequence of safe campus reopening has remained the most controversial topic in higher education since the outbreak of the COVID-19 pandemic. By the end of March 2020, almost all colleges and universities in the United States had transitioned to an all online education and many institutions have not yet fully reopened to date. For a residential campus like Stanford University, the major challenge of reopening is to estimate the number of incoming infectious students at the first day of class. Here we learn the number of incoming infectious students using Bayesian inference and perform a series of retrospective and projective simulations to quantify the risk of campus reopening. We create a physics-based probabilistic model to infer the local reproduction dynamics for each state and adopt a network SEIR model to simulate the return of all undergraduates, broken down by their year of enrollment and state of origin. From these returning student populations, we predict the outbreak dynamics throughout the spring, summer, fall, and winter quarters using the inferred reproduction dynamics of Santa Clara County. We compare three different scenarios: the true outbreak dynamics under the wild-type SARS-CoV-2, and the hypothetical outbreak dynamics under the new COVID-19 variants B.1.1.7 and B.1.351 with 56% and 50% increased transmissibility. Our study reveals that even small changes in transmissibility can have an enormous impact on the overall case numbers. With no additional countermeasures, during the most affected quarter, the fall of 2020, there would have been 203 cases under baseline reproduction, compared to 4727 and 4256 cases for the B.1.1.7 and B.1.351 variants. Our results suggest that population mixing presents an increased risk for local outbreaks, especially with new and more infectious variants emerging across the globe. Tight outbreak control through mandatory quarantine and test-trace-isolate strategies will be critical in successfully managing these local outbreak dynamics.
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During the development of the nervous system, neurons extend bundles of axons that grow and meet other neurons to form the neuronal network. Robust guidance mechanisms are needed for these bundles to migrate and reach their functional target. Directional information depends on external cues such as chemical or mechanical gradients. Unlike chemotaxis that has been extensively studied, the role and mechanism of durotaxis, the directed response to variations in substrate rigidity, remain unclear. We model bundle migration and guidance by rigidity gradients by using the theory of morphoelastic rods. We show that, at a rigidity interface, the motion of axon bundles follows a simple behavior analogous to optic ray theory and obeys Snell's law for refraction and reflection. We use this powerful analogy to demonstrate that axons can be guided by the equivalent of optical lenses and fibers created by regions of different stiffnesses.
Assuntos
Orientação de Axônios/fisiologia , Modelos Neurológicos , Rede Nervosa/crescimento & desenvolvimento , Animais , Axônios/fisiologia , Fenômenos Biomecânicos , Rede Nervosa/fisiologia , Neurônios/fisiologia , XenopusRESUMO
A central tool of nonlinear anelasticity is the multiplicative decomposition of the deformation tensor that assumes that the deformation gradient can be decomposed as a product of an elastic and an anelastic tensor. It is usually justified by the existence of an intermediate configuration. Yet, this configuration cannot exist in Euclidean space, in general, and the mathematical basis for this assumption is on unsatisfactory ground. Here, we derive a sufficient condition for the existence of global intermediate configurations, starting from a multiplicative decomposition of the deformation gradient. We show that these global configurations are unique up to isometry. We examine the result of isometrically embedding these configurations in higher-dimensional Euclidean space, and construct multiplicative decompositions of the deformation gradient reflecting these embeddings. As an example, for a family of radially symmetric deformations, we construct isometric embeddings of the resulting intermediate configurations, and compute the residual stress fields explicitly.
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The spreading of infectious diseases including COVID-19 depends on human interactions. In an environment where behavioral patterns and physical contacts are constantly evolving according to new governmental regulations, measuring these interactions is a major challenge. Mobility has emerged as an indicator for human activity and, implicitly, for human interactions. Here, we study the coupling between mobility and COVID-19 dynamics and show that variations in global air traffic and local driving mobility can be used to stratify different disease phases. For ten European countries, our study shows a maximal correlation between driving mobility and disease dynamics with a time lag of [Formula: see text] days. Our findings suggest that trends in local mobility allow us to forecast the outbreak dynamics of COVID-19 for a window of two weeks and adjust local control strategies in real time.
Assuntos
Condução de Veículo , COVID-19/epidemiologia , Surtos de Doenças , Pandemias , Viagem , Número Básico de Reprodução , Teorema de Bayes , Controle de Doenças Transmissíveis , Simulação por Computador , Europa (Continente)/epidemiologia , Sistemas de Informação Geográfica , Saúde Global , Recursos em Saúde , Humanos , Cadeias de Markov , Aprendizado SocialRESUMO
Continuum models describing ideal nematic solids are widely used in theoretical studies of liquid crystal elastomers. However, experiments on nematic elastomers show a type of anisotropic response that is not predicted by the ideal models. Therefore, their description requires an additional term coupling elastic and nematic responses, to account for aeolotropic effects. In order to better understand the observed elastic response of liquid crystal elastomers, we analyse theoretically and computationally different stretch and shear deformations. We then compare the elastic moduli in the infinitesimal elastic strain limit obtained from the molecular dynamics simulations with the ones derived theoretically, and show that they are better explained by including nematic order effects within the continuum framework.
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A hallmark of Alzheimer's disease is the aggregation of insoluble amyloid-beta plaques and tau protein neurofibrillary tangles. A key histopathological observation is that tau protein aggregates follow a structured progression pattern through the brain. Mathematical network models of prion-like propagation have the ability to capture such patterns, but a number of factors impact the observed staging result, thus introducing questions regarding model selection. Here, we introduce a novel approach, based on braid diagrams, for studying the structured progression of a marker evolving on a network. We apply this approach to a six-stage 'Braak pattern' of tau proteins, in Alzheimer's disease, motivated by a recent observation that seed-competent tau precedes tau aggregation. We show that the different modeling choices, from the model parameters to the connectome resolution, play a significant role in the landscape of observable staging patterns. Our approach provides a systematic way to approach model selection for network propagation of neurodegenerative diseases that ensures both reproducibility and optimal parameter fitting.