Simulating an in vitro experiment on nanoscale communications by using BiNS2
Introduction
Nanoscale communications is an emergent research topic, with potential applications in many fields [1], such as military usage, environmental monitoring, food control and, above all, healthcare [3], [21]. In particular, nanomedicine has achieved a lot of important results in the design of nanomachines in last decades [11]. However, the capability of coordinating the behavior of a number of nanomachines is still missing. Thus, the need of modeling information transfer at the nanoscales, especially for biological systems, requires a study able to identify the basic components of a communication system in the new environment, such as an information encoder, a transmitter, a communication medium, a receiver, and an information decoder [22], [6].
Due to the heterogeneity of different environments at nanoscales, it is unfeasible to identify general models, valid for most of nano-communication systems [1], which span from terahertz communications [25] to neuronal communications [12] to communications via diffusion of information molecules [13]. Hence, their analysis requires different models, strictly related to their environmental features. For this reason, through the combination of interdisciplinary expertise, for each area that could be involved in the research at nanoscales, it is necessary to plan and execute experiments for achieving a deep knowledge of the nanoscale environment of interest.
In this regard, simulation platforms are useful tools for gaining insight on nanoscale communications. In fact, a simulator can allow predicting the evolution of the system without having to implement it, trigger a response to an external stimulus, and observe the outcomes, thus reducing time spent and saving money [6]. Clearly, parameters and algorithms in simulators have to be accurately calibrated by matching the outcomes of real experiments with simulation results, in order to produce reliable estimates.
In this paper, we compare the experimental data of a real biological, in vitro experiment with the results of the relevant simulations obtained through the BiNS2 simulator, a Java software platform for simulating biological, nanoscale, molecular communications [10]. The experiment aims to investigate the molecular communication mechanisms between platelets and endothelium, which is of recognized importance in the study of the early stages of atherosclerosis, known as atherogenesis. The resulting communication system is composed of mobile transmitters (the platelets) which communicates through the release of specific molecules (sCD40L) with fixed receivers (the endothelial cells). The communication channel is represented by the aqueous solution (in the experiment) or by the blood in which the molecules diffuse from the transmitter to the receiver. Understanding these communication mechanisms, and in particular the minimum stimulus intensity able to activate the endothelium, is preparatory to more accurate studies involving communications inside blood vessels [9]. To simulate this experiment, the BiNS2 simulator has been enhanced with a space partition algorithm based on the octree structure [27]. This algorithm allows both exploiting the increased level of parallelism offered by modern multicore computer architectures, and scaling the simulated environment from micrometric to millimetric size, with a timescale in the order of tens of minutes.
The goal of this comparison is twofold. First, we assess the correctness of the simulation results obtained through BiNS2. Second, by matching the results of the simulations with those of the real experiment, we derive the values of some system parameters which cannot be easily obtained by means of measurements. In particular, we succeeded in estimating the numbers of receptors on the surface of endothelial cells, the receiver sensitivity, and the minimum level of the received stimulus on the endothelium able to trigger the decoding of the received signal.
In Section 2 we illustrate the background relevant to the platelet–endothelium interaction and the related works on simulating communications at the nanoscale. Section 3 presents a detailed description of the experiment, whereas Section 4 shows the relevant simulation along with numerical results. Finally, concluding remarks are sketched in Section 5.
Section snippets
Biological background
It is well known that the interaction between activated platelets and endothelium triggers the formation of atherosclerotic plaques below endothelial cells [17], [2]. When these plaques are released into the blood vessel due to a rupture of the endothelium, there is the formation of a thrombus. Activated platelets expose on their surface the CD40L cytokines [26]. The CD40L is a trimeric, transmembrane protein of the tumor necrosis factor family. Resting platelets store the CD40L inside the
Experiment set up
With reference to the communication between platelets and endothelium illustrated in Section 2.1, since 95% of circulating sCD40L is produced by platelets [2], the executed experiment aims to investigate whether platelets can activate endothelial cells without any mechanical contact, and, in that case, to what extent. Activated platelets are maintained physically separated from the endothelium by means of a membrane. The sCD40L produced by the platelet, stimulated by thrombin, reaches the
Simulation structure and results
In this section, we first briefly describe the BiNS2 simulator structure, then we describe the algorithm implemented in the BiNS2 simulator in order to scale the simulation to mimic real world experiments, and finally we illustrate the achieved results.
Conclusion
In this paper, we have shown how matching experimental data and simulation results relevant to a communications between cells can allow gaining more insights in the analyzed phenomenon. This analysis has allowed both validating the simulation reliability in order to tune our simulation platform to perform additional, more complex simulations, and deriving unknown system parameters that are fundamental for establishing a communication system at the nanoscales in the considered biological
Luca Felicetti received the master degree in Computer and Telecommunication Engineering from University of Perugia in 2011. Now, he is a Ph.D. student in Information Engineering at the Department of Electronic and Information Engineering, University of Perugia. His current research interests focus on nanoscale networking and communications.
References (28)
- et al.
Internalization of CD40 regulates its signal transduction in vascular endothelial cells
Biochemical and Biophysical Research Communications
(2006) - et al.
A simulation tool for nanoscale biological networks
Nano Communication Networks
(2012) - et al.
Simulation of molecular signaling in blood vessels: software design and application to atherogenesis
Nano Communication Networks
(2013) - et al.
Diffusion-based physical channel identification in molecular nanonetworks
Nano Communication Networks
(2011) - et al.
NanoNS: a nanoscale network simulator framework for molecular communications
Nano Communication Networks
(2010) - et al.
CD40 signaling in vascular cells: a key role in atherosclerosis?
Atherosclerosis
(1998) - et al.
Molecular communication nanonetworks inside human body
Nano Communication Networks Journal
(2012) - et al.
The internet of nano-things
IEEE Wireless Communications Magazine
(2010) - et al.
Platelet-derived CD40L: the switch-hitting player of cardiovascular disease
Circulation
(2002) - et al.
Body area nanonetworks with molecular communications in nanomedicine
IEEE Communications Magazine
(2012)
The CD40 antigen and its ligand
Annual Review of Immunology
Modeling the spontaneous reaction of mammalian cells to external stimuli
Targeting CD40L: a promising therapeutic approach
Clinical and Diagnostic Laboratory Immunology
Cited by (30)
The effective geometry Monte Carlo algorithm: Applications to molecular communication
2019, Physics Letters, Section A: General, Atomic and Solid State PhysicsCitation Excerpt :Although analytical results are derived for some simple diffusion channels, such as a point transmitter and a spherical absorbing receiver in an unbounded environment [4] and in bounded environments [5,6], a deeper analysis including more complicated structures requires fast and reliable simulations of sophisticated diffusion channels. To meet this demand, many different simulation frameworks have been proposed in the literature, such as N3Sim [7], NanoNS [8], BiNS2 [9] and AcCoRD [10]. The most simple algorithm performing diffusion channel simulations is usually referred to as a Monte Carlo (MC) simulation algorithm.
Parallel algorithms for simulating interacting carriers in nanocommunication
2019, Nano Communication NetworksCitation Excerpt :A set of customization tools is included, allowing to create objects and model the behavior and interactions of biological entities (e.g. partial inelastic collisions). A combination of octree and the sort-and-sweep algorithm [20] is used to detect both inter-carriers collisions and collisions between carriers and transceivers in a computationally efficient way. A more detailed description of the octree algorithm of this Java-based simulator is provided in Section 5.4.
The Molecular Communications Markup Language (MolComML)
2018, Nano Communication NetworksCitation Excerpt :For example, the existing MolCom simulators, such as BiNS2 [3], N3Sim [4] or other ones based on NS3 [5], include functions for simulating diffusion-based channels. They can be configured by using different configuration interfaces and generate different output files, which makes difficult to compare simulation results, especially for complex scenarios [6,7]. This paper introduces an efficient solution for the reproducibility of results, whether they are obtained by either numerical analysis or experimental synthesis, by means of a flexible XML-based [8] markup language, called MolComML (Molecular Communication Markup Language).
Applications of molecular communications to medicine: A survey
2016, Nano Communication NetworksCitation Excerpt :A further development could be the in-silico emulation of the process of artery narrowing, which can have a major effect on blood flow, ultimately leading to the total closure of vessels that may cause diseases such as, angina, myocardial infarction, stroke, and critical limb ischemia, depending on the site of the atheroma. Clearly, the in-silico emulation has to be previously tuned by means of the analysis of the outcomes of a number of in-vitro/in-vivo experiments [44,45,40], in order to validate the simulation platform, and to make it so robust to be easily parameterized by means of a limited number of parameters, which can be extracted by standard lab examinations. Fig. 4 shows the mapping of traditional communications systems elements onto the biological ones [45].
Simulation study of molecular communication systems with an absorbing receiver: Modulation and ISI mitigation techniques
2014, Simulation Modelling Practice and TheoryCitation Excerpt :BINS is upgraded to BINS2, which offers new feature to simulate bounded environments. Using the BINS2 simulator, propagation in blood vessels is analyzed in [31] and in vitro experiments are simulated in [32]. In this paper, a modular and an end-to-end MolecUlar CommunicatIoN (MUCIN) simulator is presented.
Digital Communication Techniques in Macroscopic Air-Based Molecular Communication
2022, IEEE Transactions on Molecular, Biological, and Multi-Scale Communications
Luca Felicetti received the master degree in Computer and Telecommunication Engineering from University of Perugia in 2011. Now, he is a Ph.D. student in Information Engineering at the Department of Electronic and Information Engineering, University of Perugia. His current research interests focus on nanoscale networking and communications.
Mauro Femminella received both the master degree and the Ph.D. in Electronic Engineering from University of Perugia in 1999 and 2003, respectively. Since November 2006, he is assistant professor at the Department of Electronic and Information Engineering, University of Perugia. His current research interests focus on nanoscale networking and communications, middleware platforms for multimedia services, location and navigation systems, and network and service management architectures for the Future Internet.
Gianluca Reali is an associate professor at the University of Perugia, Department of Information and Electronic Engineering (DIEI), Italy, since January 2005. He received the Ph.D. degree in Telecommunications from the University of Perugia in 1997. From 1997 to 2004 he was researcher at DIEI. In 1999 he visited the Computer Science Department at UCLA. His research activities include resource allocation over packet networks, wireless networking, network management, and multimedia services.
Paolo Gresele is an associate professor of Internal Medicine at the University of Perugia since November 2001. In September 2010 he has won the contest for the full professor of Internal Medicine at University of Turin. Education: School of Medicine at the University of Perugia (Italy) (1972–1978); M.D. degree with the highest marks (110/110 cum laude) presenting a thesis on “Thrombolytic therapy of pulmonary embolism”. Specialization in Internal Medicine at the University of Perugia Medical School (1979–1984) cum laude. Ph.D. Degree in Medical Sciences at the University of Leuven (Belgium) on 01/06/1987; Title of “Dottore di Ricerca” (Research Doctorate) from the Italian Ministry of Public Education on 19/10/1988.
Main research topics: Hemostasis in neoplastic patients; Antiplatelet therapy; Pharmacology of platelet function inhibition; Role of platelet in asthma and inflammation; Platelet receptors; Physiopathology of platelet signal transduction; Arachidonic acid metabolism in gastroenterology; Hereditary thrombocytopenia diseases; Peripheral Arterial Disease: physiopathology and therapy; Endothelial dysfunction; Development of animal models of atherosclerosis and thrombosis. Publications:Author, or coauthor, of 185 original papers, 29 books chapters, 338 abstracts at national and international congress; Impact Score: 1205,904; average Impact Factor: 7.30; 5495 Citations from the Science Citation Index at 06/06/2013, H-index 37.
Editor of the books: “Platelets in thrombotic and non-thrombotic disorders”, Cambridge University Press, Cambridge 2002; “Platelets in Cardiovascular and Hematologic Disorders: a clinical handbook”, Cambridge University Press, Cambridge 2008; “Antiplatelet Agents”, Springer Verlag 2013.
Marco Malvestiti received the master degree in Medical Biotechnology from University of Perugia in 2009. Now, he is a Ph.D. student in Bioscience, Biotechnology and Biomaterials in Vascular and Metabolic Diseases at University of Perugia. In Spring 2010 he spent a research period at King’s College, London (UK), under the guidance of Prof. Albert Ferro.