“Nanoscale and Molecular Networking,” IEEE Journal on Selected Areas in Communications, vol. 31, no. 12, December 2013.

S.F. Bush, Nanoscale Communication Networks, Artech House, 2010.

This book deals with nanoscale communication networks, covering both dry (non-biological) and wet (biological) communication paradigms. The book is a good reference for researchers who would like to work in this field of research in the future. Considering the highly interdisciplinary nature of this field of research, the book lists most of the related papers in the field.

T. Nakano, A.W. Eckford, and T. Haraguchi, Molecular Communication, Cambridge University Press, 2013.

This is another good book on nanoscale communication systems. The book focuses more narrowly upon molecular communication, i.e., the wet communication paradigm. Since molecular communication is thought of as one of the possible physical layers for nanoscale networks, the concepts and theories presented in this book should be useful to researchers who will be working on molecular nanoscale networks in the future.

T. Nakano, T. Suda, Y. Okaie, M.J. Moore, and A.V. Vasilakos, “Molecular Communication Among Biological Nanomachines: A Layered Architecture and Research Issues,” IEEE Transactions on NanoBioscience, vol. 13, no. 3, pp. 169-197, September 2014.

This is a good piece of work in the field of molecular communication. This paper presents a layered architecture of molecular communication. This paper is well written by experts in this field. Based on the similarity of layered concepts in traditional communication networks, the paper proposes a similar layered approach to molecular communication system. In addition, the paper discusses the layers in detail with descriptive models, functionalities, and research issues involved. The paper also presents a design example of a potential molecular communication application in targeted drug delivery system based on molecular communication approach in detail with its system design, analytical model, and numerical results that should be useful to researchers in this field. As a whole, the paper has discussed molecular communication and its current research questions and is able to provide future research directions in this field. The paper stands as a guidance to all researchers in this field, and therefore, should be considered as a useful piece of work in this new field of molecular communication nanonetworks.

M.J. Moore, T. Suda, and K. Oiwa, “Molecular Communication: Modeling Noise Effects on Information Rate,” IEEE Transactions on NanoBioscience, vol. 8, no. 2, pp. 169-180, June 2009.

This paper reviews molecular communication systems and investigates the probability of information molecules reaching a nanoscale receiver and the information rate. The paper makes a useful analysis of noise effects in molecular communication where the molecules are transported from the transmitter to the receiver by either diffusion-based propagation or walkway-based molecular motors. Noise reduction approaches, based on exponential decay and receiver-removal of molecules, have been addressed. Both a single communication link and a broadcast communication system have been investigated. The paper also describes a simulation model and presents numerical results in order to explain the effects of noise on the performance of the system. The results presented in this paper are able to provide fundamentals of molecular communication principles to researchers from interdisciplinary backgrounds as well as practicing engineers. The paper is well written and provides a good understanding of the noise effects on the information rate in molecular communication systems.

M. S. Islam and V.J. Logeeswaran, “Nanoscale Materials and Devices for Future Communication Networks,” IEEE Communications Magazine, vol. 48, no. 6, pp. 112-120, June 2010.

This article presents developments in nanoscale materials that have the potential to play a critical role in the transformation of future intelligent communication networks. New discoveries in materials on the nanometer-length scale are expected to play an important role in addressing ongoing and future challenges in the field of communication. Devices and systems for ultra-high-speed short and long-range communication links, portable and power-efficient computing devices, high density memory and logic, ultra-fast interconnects, and autonomous and robust energy scavenging devices for accessing ambient intelligence and needed information will critically depend on the success of next-generation emerging nanoscale materials and devices.

IEEE P1906.1 — Draft Recommended Practice for Nanoscale and Molecular Communication Framework.

IEEE P1906.1 is an IEEE standards working group sponsored by the IEEE Communications Society Standards Development Board whose goal is to develop a definition and common framework for nanoscale and molecular communication. Because this is an emerging technology, the standard is meant to elicit innovation by determining a common definition, terminology, framework, goals, metrics, and use-cases designed to encourage greater innovation and enable the technology to advance at a faster rate. The standard defines the fundamental definition and building blocks of nanoscale communications.

T.A. Sanders, E. Llagostera, and M. Barna, “Specialized Filopodia Direct Long-range Transport of SHH During Vertebrate Tissue Patterning,” Nature, vol. 497, no. 7451, pp. 628–632, 30 May 2013.

Cells were thought to communicate either by long-range secretion-reception signaling (diffusion dependent) or by direct contact between adjacent cells. Sanders et al. showed that mesenchymal cells can form 100 µm-long and 200 nm-thin tube-like structures and collect important signaling molecules far from where they reside. Receptors can travel along these protrusions at 100 nm/s.

S. Roy, H. Huang, S. Liu, and T.B. Kornberg, “Cytoneme-Mediated Contact-Dependent Transport of the Drosophila Decapentaplegic Signaling Protein,” Science, vol. 343, no. 6173, 21 February 2014.

Roy et al. described similar structures, although in distinct cell types, that were also involved in receptor transport over long distances. Interestingly they showed that these protrusions were not collecting every surrounding signal but specifically the receptors from the cells reached by the tip of the protrusions, a very selective, directed and long-range communication process. Both this paper and the previous paper considerably extend our appreciation of the mechanisms supporting communication-based morphogenesis in biology.

L. Bardwell, X. Zou, Q. Nie, and N. L. Komarova, “Mathematical Models of Specificity in Cell Signaling,” Biophysical Journal, vol. 92, no. 10, pp. 3425-3441, 15 May 2007.

This paper helps readers to understand the characterization of the mathematical models of simple signaling networks. This model derives exact analytical expressions for two measures of cross talk called specificity and fidelity. The performance of several insulating mechanisms--combinatorial signaling, compartmentalization, the inhibition of one pathway by another, and the selective activation of scaffold proteins--is evaluated with respect to the trade-off between the specificity they provide and the constraints they place on the network. Cellular signaling pathways transduce extracellular signals into appropriate responses. These pathways are typically interconnected to form networks, often with different pathways sharing similar or identical components. A consequence of this connectedness is the potential for cross talk, some of which may be undesirable. Indeed, experimental evidence indicates that cells have evolved insulating mechanisms to partially suppress “leaking” between pathways. The effects of noise are also considered.

I.V. Dokukina, M.E. Gracheva, E.A. Grachev, and J.D. Gunton, “Role of Network Connectivity in Intercellular Calcium Signaling,” Physica D: Nonlinear Phenomena, vol. 237, no. 6, pp. 745-754, 15 May 2008.

This work helps readers to understand the importance of the topology of intercellular connectivity by investigating the properties of a model of Ca2+ signaling for a small number of connected cells. It is important to understand the coordinated performance of cells in tissue. One possible mechanism in this coordination involves intracellular Ca2+ signaling. The topology of intercellular connections in tissue should also play an important role in this process. It is most relevant for plane tissues, in which the interaction between cells is due to gap junctions (epithelium, blood vessels).

S. Schuster, M. Marhl, and T. Hofer, “Modelling of Simple and Complex Calcium Oscillations,” European Journal of Biochemistry, vol. 269, no. 5, pp. 1333-1355, March 2002.

This paper provides a review with a comparative overview of recent developments in the modeling of cellular calcium oscillation. A large variety of mathematical models have been developed for this widespread phenomenon in intra- and intercellular signaling. From these, a general model is extracted that involves six types of concentration variables: inositol 1,4,5-trisphosphate (IP3), cytoplasmic, endoplasmic reticulum and mitochondrial calcium, the occupied binding sites of calcium buffers, and the fraction of active IP3 receptor calcium release channels. Using this framework, the models of calcium oscillations can be classified into “minimal” models containing two variables and “extended” models of three or more variables. Three types of minimal models are identified that are all based on calcium-induced calcium release (CICR), but differ with respect to the mechanisms limiting CICR.

Y. Tang and H.G. Othmer, “Frequency Encoding in Excitable Systems with Applications to Calcium Oscillations,” Proceedings of the National Academy of Sciences, vol. 29, no. 17, pp. 7869-7873, 15 August 1995.

This paper helps the reader to understand the development of a theory of frequency encoding in excitable systems and apply it to intracellular calcium oscillation that results from increases in the intracellular level of inositol 1,4,5-trisphosphate. A number of excitable cell types respond to a constant hormonal stimulus with a periodic oscillation in intracellular calcium. The frequency of oscillation is often proportional to the hormonal stimulus and leads to the notion of frequency encoding.

W.H. Bossert, and E.O. Wilson, “The Analysis of Olfactory Communication Among Animals,” Journal of Theoretical Biology, vol. 5, no. 3, pp. 443–469, November 1963.

The paper introduces and discusses methods for determining those parameters of olfactory communication systems most closely related to the diffusion process, which in turns shed lights on the principles to be applied for molecular-diffusion processes. In addition to four general cases of diffusion considered in the paper, three real communication systems, involving an alarm substance, a recruitment trail, and a sex attractant are analyzed and explained. The paper provides a technical and extensive studies on techniques that could potentially benefit other interested researchers in the upcoming domain of nano-scale and small-scale communication systems specifically applying molecular diffusion methods.

I. Llatser, A. Cabellos-Aparicio, and E. Alarcon, “Networking Challenges and Principles in Diffusion-Based Molecular Communication,” IEEE Wireless Communications, vol. 19, no. 5, pp. 36-41, October 2012.

Diffusion-based molecular (DMC) communication networks are described and analyzed ion this paper. It presents some of the most relevant design challenges and principles that will potentially influence future DMC networks. One important factor to consider when referring to this paper and applying its principles is a few assumptions have been taken to make the analysis more general and applicable to wider domains. The paper also summarizes differences between DMC and electromagnetic-based communications including propagation delay, channel distortion, and node mobility. The presented results provide useful guidelines for designers of future DMC networks.

S. Kadloor, R.S. Adve, and A.W. Eckford, “Molecular Communication Using Brownian Motion with Drift,” IEEE Transactions on NanoBioscience, vol. 11, no. 2, pp. 89-99, June 2012.

Inspired by biological communication systems, molecular communication has been proposed as a viable scheme to communicate between nanoscale sized devices separated by a very short distance. Here, molecules are released by the transmitter into the medium, which are then sensed by the receiver. This paper develops a preliminary version of such a communication system focusing on the release of either one or two molecules into a fluid medium with drift. The authors analyze the mutual information between the transmitter and receiver when information is encoded in the time of release of the molecule. Simplifying assumptions are used in order to calculate the mutual information, and theoretical results are provided to show that these calculations are upper bounds on the true mutual information. Furthermore, optimized degree distributions are provided, which suggest transmission strategies for a variety of drift velocities.

K. Francis and B.O. Palsson, “Effective Intercellular Communication Distances are Determined by the Relative Time Constants for Cyto/Chemokine Secretion and Diffusion,” Proceedings of the National Academy of Sciences, vol. 94, no. 23, pp. 12258-12262, 11 November 1997.

This work helps the reader to understand a solitary cell model to estimate effective communication distances over which a single cell can meaningfully propagate a soluble signal. A cell’s ability to effectively communicate with a neighboring cell is essential for tissue function and ultimately for the organism to which it belongs. One important mode of intercellular communication is the release of soluble cyto- and chemokines. Once secreted, these signaling molecules diffuse through the surrounding medium and eventually bind to neighboring cell’s receptors whereby the signal is received. This mode of communication is governed both by physicochemical transport processes and cellular secretion rates, which in turn are determined by genetic and biochemical processes. The characteristics of transport processes have been known for some time, and information on the genetic and biochemical determinants of cellular function is rapidly growing. Simultaneous quantitative analysis of the two is required to systematically evaluate the nature and limitations of intercellular signaling. This analysis reveals that: (i) this process is governed by a single, key, dimensionless group that is a ratio of biological parameters and physicochemical determinants; (ii) this ratio has a maximal value; (iii) for realistic values of the parameters contained in this dimensionless group, it is estimated that the domain that a single cell can effectively communicate in is > 250 mm in size; and (iv) the communication within this domain takes place in 10–30 minutes. These results have fundamental implications for interpretation of organ physiology and for engineering tissue function ex vivo.

S. Klumpp, T.M. Nieuwenhuizen, and R. Lipowsky, “Self-Organized Density Patterns of Molecular Motors in Arrays of Cytoskeletal Filaments,” Biophysical Journal, vol. 88, no. 5, pp. 3118-32, May 2005.

This work helps the reader understand the use of Monte Carlo simulations and a two-state model in the stationary states of systems with many molecular motors for uniaxial and centered (aster-like) arrangements of cytoskeletal filaments. Mutual exclusion of motors from binding sites of the filaments is taken into account. For small overall motor concentration, the density profiles are exponential and algebraic in uniaxial and centered filament systems, respectively. For uniaxial systems, exclusion leads to the coexistence of regions of high and low densities of bound motors corresponding to motor traffic jams, which grow upon increasing the overall motor concentration. These jams are insensitive to the motor behavior at the end of the filament. In centered systems, traffic jams remain small and an increase in the motor concentration leads to a flattening of the profile if the motors move inwards and to the buildup of a concentration maximum in the center of the aster if motors move outwards. In addition to motor density patterns, the authors also determine the corresponding patterns of the motor current.

N. Farsad, A.W. Eckford, and S. Hiyama, “A Markov Chain Channel Model for Active Transport Molecular Communication,” IEEE Transactions on Signal Processing, vol. 62, no. 9, pp. 2424-2436, May 2014.

The paper introduces a Markov model, which can be used to reduce the amount of simulation necessary to study the motion of information molecules in active transport schemes without sacrificing accuracy. The model can be used to calculate parameters such as channel capacity accurately and in a timely manner, using data from real experiments.

S. Balasubramaniam and P. Lio, “Multi-Hop Conjugation Based Bacteria Nanonetworks,” IEEE Transactions on NanoBioscience, vol. 12, no. 1, pp. 47-59, March 2013.  

This paper analyzes multi-hop molecular nanoscale networks that utilize bacteria for moving DNA-based information. The approach illustrated in the paper combines different properties of bacteria to enable multi-hop transmission, such as conjugation and chemotaxis-based motility. The paper suggests that numerous bacteria properties fit to properties required for communication networking (e.g., packet filtering, routing, addressing).

Y. Chahibi, M. Pierobon, S.O. Song, and I.F. Akyildiz, “A Molecular Communication System Model for Particulate Drug Delivery Systems,” IEEE Transactions on Biomedical Engineering, vol. 60, no. 12, pp. 3468-3483, December 2013.

This paper presents a comprehensive molecular communication channel model of drug particle propagation through the cardiovascular system. Two separate contributions within the model were identified, namely, the cardiovascular network model and the drug propagation network model. The cardiovascular network model allows analytical computation of the blood velocity profile in every location of the cardiovascular system from the knowledge of the blood pressure profile and flowing input from the heart. The drug propagation network model allows computation of the drug delivery rate at the targeted site from knowledge of the location of the injection and the injection rate profile. The derived model takes into account individual specificities in the physiological parameters of the cardiovascular system, such as the compliance of the blood vessels, the heartbeat rate profile, and the heartbeat stroke volume. The proposed model opens up the possibility to study optimization techniques for particulate drug delivery systems.

N. Farsad, A.W. Eckford, S. Hiyama, and Y. Moritani, “On-Chip Molecular Communication: Analysis and Design,” IEEE Transactions on NanoBioscience, vol. 11, no. 3, pp. 304-314, September 2012.

This paper addresses another major molecular communication medium, a confined-space microfluidic chip. Brownian motion (passive transport), Brownian motion with flow (active transport using an external device), and molecular motor based active transport propagation schemes were considered. Both passive and active propagation schemes were compared and analyzed by deriving a set of tools to measure the achievable information rates of the on-chip molecular communication systems. A simulation toolbox for estimation of channel capacity based on Monte Carlo techniques was developed. This toolbox was used to optimize design parameters such as the shape of the transmission area to increase the information rate. Furthermore, the effect of separation distance between the transmitter and the receiver on information rate was examined under both propagation schemes, and a guidepost to design an optimal molecular communication setup and protocol was presented.