Elsevier

Nano Communication Networks

Volume 4, Issue 4, December 2013, Pages 172-180
Nano Communication Networks

Simulating an in vitro experiment on nanoscale communications by using BiNS2

https://doi.org/10.1016/j.nancom.2013.08.003Get rights and content

Abstract

Nanoscale communications is an emergent research topic with potential applications in many fields. In order to design nanomachines able to exploit the communication potentials of nanoscale environments, it is necessary to identify the basic communication mechanisms and the relevant parameters. In this paper, we show how system parameters can be derived by suitably matching the results of in vitro experiments with those obtained via simulations by using the BiNS2 simulator. In order to scale the simulation from micrometric settings, with timescale in the order of seconds, to real experiments lasting tens of minutes with millimetric size, we enhanced the BiNS2 simulator by introducing a space partition algorithm based on the octree. In this way, the simulator can exploit the high level of parallelism of modern multicore computer architectures. We have used this technique for simulating an experiment focused on the communication between platelets and endothelium through the diffusion of nanoparticles. Simulation results match experimental data, thus allowing us to infer useful information on the receiver operation.

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.

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    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.

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