Simulation of molecular signaling in blood vessels: Software design and application to atherogenesis

Abstract

This paper presents a software platform, named BiNS2, able to simulate diffusion-based molecular communications with drift inside blood vessels. The contribution of the paper is twofold. First a detailed description of the simulator is given, under the software engineering point of view, by highlighting the innovations and optimizations introduced. Their introduction into the previous version of the BiNS simulator was needed to provide to functions for simulating molecular signaling and communication potentials inside bounded spaces. The second contribution consists of the analysis, carried out by using BiNS2, of a specific communication process happening inside blood vessels, the atherogenesis, which is the initial phase of the formation of atherosclerotic plaques, due to the abnormal signaling between platelets and endothelium. From a communication point of view, platelets act as mobile transmitters, endothelial cells are fixed receivers, sticky to the vessel walls, and the transmitted signal is made of bursts of molecules emitted by platelets. The simulator allows evaluating the channel latency and the footprint on the vessel wall of the transmitted signal as a function of the transmitter distance from the vessels wall, the signal strength, and the receiver sensitivity. IntroductionThe capabilities of manipulating matter at the molecular scale has inspired a huge research effort for many years and has led to the design of sophisticated devices, commonly referred to as nanomachines. The potentials of these nano-devices span numerous areas [1][8][13], including medical science [2][14], environmental control, and material science. The technological progress has stimulated a lot of research focusing on different types of nanomachines, such as those related to the usage of carbon nanotubes and nanowires [51], and those making use of biological methods, which are the object of our analysis. Although full-fledged biological nanomachines do not yet exist, recently biochemists have done many progresses in this area, and now they are able to create at least functional cell components, such as artificial ribosomes, which can be used for the synthesis of proteins [49][50].However, the research regarding nanomachine networked coordination is still at an early stage.In the last years, some possible solutions for allowing nanomachines to exchange information have been proposed [1]. Clearly, achieving the objective of exchanging information at the nanoscale requires a deep exploration of the feasible mechanisms that allow designing the basic components of a communications system, such as an information encoder, a transmitter, a communication medium, a receiver, and an information decoder [13].Due to the heterogeneity of different environments and communication techniques that can be used at the nanoscale, it is unfeasible to identify general models, valid for most of nanocommunication systems. For example, signaling within a lymph node, or within blood vessels, or between brain cells, make use of mechanisms specific for each ...

Modeling CD40-Based Molecular Communications in Blood Vessels

“…Simulation have been carried out by means of the BINS simulator [7], which is customizable in order to be useful for several molecular simulation scenarios. In order to confine the simulations within the blood vessel, in [23] we have introduced the possibility to bound the simulation within a cylinder. By using this extended simulation model, it is possible to simulate a short section of the venule, modeling also cells entering and exiting from the vessel section in order to maintain the desired velocity profile and particle concentration.…”

“…The approach of BiNS, further improved in [23], [24], is fine grained in that the position of each element is evaluated at each simulation step, and collisions are managed according to an elastic model. In the model, receptors are distributed over the surface of each fixed or mobile nano machine.…”

Channel Modeling for Diffusive Molecular Communication—A Tutorial Review

“…Mature tools from the physical chemistry community include Smoldyn (see [69], [129]). Microscopic tools that have been developed specifically for the MC community include BiNS2 [130], N3Sim [131], MUCIN [92], and AcCoRD [119].…”

“…However, some important MC environments, such as the cardiovascular system, are quite complex and cannot be fully modeled based on physics' first principals. One approach is to develop simulation environments for such complex networks, see [130] and Section V-A. Nevertheless, for system design, it is desirable to have simple yet sufficiently accurate analytical models for complex multi-node networks.…”

On the Interaction between a Nanoparticulate System and the Human Body in Body Area Nanonetworks

“…In [23], Felicetti et al provide a software platform, named BiNS2, able to simulate diffusion-based molecular communications inside blood vessels, in order to analyze the interactions of nanoparticles with the blood cells. The same simulator is also exploited in [24], where the authors describe a specific communication process happening inside blood vessels, atherogenesis. Another similar paper is [25], where a particle-cell hybrid model is developed to model nanoparticle transport, dispersion and binding dynamics in the blood.…”