Fractional-order susceptible-infected model: definition and applications to the study of COVID-19 main protease

We propose a model for the transmission of perturbations across the amino acids of a protein represented as an interaction network. The dynamics consists of a Susceptible-Infected (SI) model based on the Caputo fractional-order derivative. We find an upper bound to the analytical solution of this model which represents the worse-case scenario on the propagation of perturbations across a protein residue network. This upper bound is expressed in terms of Mittag-Leffler functions of the adjacency matrix of the network of inter-amino acids interactions. We then apply this model to the analysis of the propagation of perturbations produced by inhibitors of the main protease of SARS CoV-2. We find that the perturbations produced by strong inhibitors of the protease are propagated far away from the binding site, confirming the long-range nature of intra-protein communication. On the contrary, the weakest inhibitors only transmit their perturbations across a close environment around the binding site. These findings may help to the design of drug candidates against this new coronavirus.Comment: 21 pages, 2 figure

Metaplex networks: influence of the exo-endo structure of complex systems on diffusion

In a complex system the interplay between the internal structure of its entities and their interconnection may play a fundamental role in the global functioning of the system. Here, we define the concept of metaplex, which describes such trade-off between internal structure of entities and their interconnections. We then define a dynamical system on a metaplex and study diffusive processes on them. We provide analytical and computational evidences about the role played by the size of the nodes, the location of the internal coupling areas, and the strength and range of the coupling between the nodes on the global dynamics of metaplexes. Finally, we extend our analysis to two real-world metaplexes: a landscape and a brain metaplex. We corroborate that the internal structure of the nodes in a metaplex may dominate the global dynamics (brain metaplex) or play a regulatory role (landscape metaplex) to the influence of the interconnection between nodes.Comment: 28 pages, 19 figure

Fractional Patlak-Keller-Segel equations for chemotactic superdiffusion

The long range movement of certain organisms in the presence of a chemoattractant can be governed by long distance runs, according to an approximate Levy distribution. This article clarifies the form of biologically relevant model equations: We derive Patlak-Keller-Segel-like equations involving nonlocal, fractional Laplacians from a microscopic model for cell movement. Starting from a power-law distribution of run times, we derive a kinetic equation in which the collision term takes into account the long range behaviour of the individuals. A fractional chemotactic equation is obtained in a biologically relevant regime. Apart from chemotaxis, our work has implications for biological diffusion in numerous processes.Comment: 20 pages, 4 figures, to appear in SIAM Journal on Applied Mathematic

Macroscopic limit of a kinetic model describing the switch in T cell migration modes via binary interactions

Experimental results on the immune response to cancer indicate that activation of cytotoxic T lymphocytes (CTLs) through interactions with dendritic cells (DCs) can trigger a change in CTL migration patterns. In particular, while CTLs in the pre-activation state move in a non-local search pattern, the search pattern of activated CTLs is more localised. In this paper, we develop a kinetic model for such a switch in CTL migration modes. The model is formulated as a coupled system of balance equations for the one-particle distribution functions of CTLs in the pre-activation state, activated CTLs and DCs. CTL activation is modelled via binary interactions between CTLs in the pre-activation state and DCs. Moreover, cell motion is represented as a velocity-jump process, with the running time of CTLs in the pre-activation state following a long-tailed distribution, which is consistent with a L\'evy walk, and the running time of activated CTLs following a Poisson distribution, which corresponds to Brownian motion. We formally show that the macroscopic limit of the model comprises a coupled system of balance equations for the cell densities whereby activated CTL movement is described via a classical diffusion term, whilst a fractional diffusion term describes the movement of CTLs in the pre-activation state. The modelling approach presented here and its possible generalisations are expected to find applications in the study of the immune response to cancer and in other biological contexts in which switch from non-local to localised migration patterns occurs.Comment: 21 pages, 1 figur

Interacting particles with L\'{e}vy strategies: limits of transport equations for swarm robotic systems

L\'{e}vy robotic systems combine superdiffusive random movement with emergent collective behaviour from local communication and alignment in order to find rare targets or track objects. In this article we derive macroscopic fractional PDE descriptions from the movement strategies of the individual robots. Starting from a kinetic equation which describes the movement of robots based on alignment, collisions and occasional long distance runs according to a L\'{e}vy distribution, we obtain a system of evolution equations for the fractional diffusion for long times. We show that the system allows efficient parameter studies for a search problem, addressing basic questions like the optimal number of robots needed to cover an area in a certain time. For shorter times, in the hyperbolic limit of the kinetic equation, the PDE model is dominated by alignment, irrespective of the long range movement. This is in agreement with previous results in swarming of self-propelled particles. The article indicates the novel and quantitative modeling opportunities which swarm robotic systems provide for the study of both emergent collective behaviour and anomalous diffusion, on the respective time scales.Comment: 23 pages, 3 figures, to appear in SIAM Journal on Applied Mathematic

Asymptotic preserving schemes for nonlinear kinetic equations leading to volume-exclusion chemotaxis in the diffusive limit

In this work we first prove, by formal arguments, that the diffusion limit of nonlinear kinetic equations, where both the transport term and the turning operator are density-dependent, leads to volume-exclusion chemotactic equations. We generalise an asymptotic preserving scheme for such nonlinear kinetic equations based on a micro-macro decomposition. By properly discretizing the nonlinear term implicitly-explicitly in an upwind manner, the scheme produces accurate approximations also in the case of strong chemosensitivity. We show, via detailed calculations, that the scheme presents the following properties: asymptotic preserving, positivity preserving and energy dissipation, which are essential for practical applications. We extend this scheme to two dimensional kinetic models and we validate its efficiency by means of 1D and 2D numerical experiments of pattern formation in biological systems.Comment: 30 pages, 8 figure

Space-time fractional diffusion in cell movement models with delay

The movement of organisms and cells can be governed by occasional long distance runs, according to an approximate L\'evy walk. For T cells migrating through chronically-infected brain tissue, runs are further interrupted by long pauses, and the aim here is to clarify the form of continuous model equations which describe such movements. Starting from a microscopic velocity-jump model based on experimental observations, we include power-law distributions of run and waiting times and investigate the relevant parabolic limit from a kinetic equation for resting and moving individuals. In biologically relevant regimes we derive nonlocal diffusion equations, including fractional Laplacians in space and fractional time derivatives. Its analysis and numerical experiments shed light on how the searching strategy, and the impact from chemokinesis responses to chemokines, shorten the average time taken to find rare targets in the absence of direct guidance information such as chemotaxis.Comment: 25 pages, 8 figures, Mathematical Models and Methods in Applied Sciences (2019

What Is in a Simplicial Complex? A Metaplex-Based Approach to Its Structure and Dynamics

Geometric realization of simplicial complexes makes them a unique representation of complex systems. The existence of local continuous spaces at the simplices level with global discrete connectivity between simplices makes the analysis of dynamical systems on simplicial complexes a challenging problem. In this work, we provide some examples of complex systems in which this representation would be a more appropriate model of real-world phenomena. Here, we generalize the concept of metaplexes to embrace that of geometric simplicial complexes, which also includes the definition of dynamical systems on them. A metaplex is formed by regions of a continuous space of any dimension interconnected by sinks and sources that works controlled by discrete (graph) operators. The definition of simplicial metaplexes given here allows the description of the diffusion dynamics of this system in a way that solves the existing problems with previous models. We make a detailed analysis of the generalities and possible extensions of this model beyond simplicial complexes, e.g., from polytopal and cell complexes to manifold complexes, and apply it to a real-world simplicial complex representing the visual cortex of a macaque.M.M. and E.E. acknowledge support from Project OLGRA (PID2019-107603GB-I00) funded by the Spanish Ministry of Science and Innovation, as well as by the Maria de Maeztu project CEX2021-001164-M funded by the MCIN/AEI/10.13039/501100011033. G.E.-R acknowledges support from the project macroKNIGHTs (PID2022-143012NA-100) funded by the Spanish Ministry of Science and Innovation.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001164-M).Peer reviewe