Molecular Communication Research Articles

Molecular Communication for Quorum Sensing Inspired Cooperative Drug Delivery

A cooperative drug delivery system is proposed, where quorum sensing (QS), a density-dependent bacterial behavior coordination mechanism, is employed by synthetic bacterium-based nanomachines (B-NMs) for controllable drug delivery. In our proposed system, drug delivery is only triggered when there are enough QS molecules, which in turn only happens when there are enough B-NMs. This makes the proposed system can be used to achieve a high release rate of drug molecules from a high number of B-NMs when the population density of B-NMs may not be known. Analytical expressions for i) the expected activation probability of the B-NM due to randomly-distributed B-NMs and ii) the expected aggregate absorption rate of drug molecules due to randomly-distributed QS activated B-NMs are derived. Analytical results are verified by particle-based simulations. The derived results can help to predict and control the impact of environmental factors (e.g., diffusion coefficient and degradation rate) on the absorption rate of drug molecules since rigorous diffusion-based molecular channels are considered. Our results show that the activation probability at the B-NM increases as this B-NM is located closer to the center of the B-NM population and the aggregate absorption rate of the drug molecules non-linearly increases as the population density increases.

CD11c+ microglia promote white matter repair after ischemic stroke

Ischemic stroke leads to white matter damage and neurological deficits. However, the characteristics of white matter injury and repair after stroke are unclear. Additionally, the precise molecular communications between microglia and white matter repair during the stroke rehabilitation phase remain elusive. In this current study, MRI DTI scan and immunofluorescence staining were performed to trace white matter and microglia in the mouse transient middle cerebral artery occlusion (tMCAO) stroke model. We found that the most serious white matter damage was on Day 7 after the ischemic stroke, then it recovered gradually from Day 7 to Day 30. Parallel to white matter recovery, we observed that microglia centered around the damaged myelin sheath and swallowed myelin debris in the ischemic areas. Then, microglia of the ischemic hemisphere were sorted by flow cytometry for RNA sequencing and subpopulation analysis. We found that CD11c+ microglia increased from Day 7 to Day 30, demonstrating high phagocytotic capabilities, myelin-supportive genes, and lipid metabolism associated genes. CD11c+ microglia population was partly depleted by the stereotactic injecting of rAAV2/6M-taCasp3 (rAAV2/6M-CMV-DIO-taCasp3-TEVp) into CD11c-cre mice. Selective depletion of CD11c+ microglia disrupted white matter repair, oligodendrocyte maturation, and functional recovery after stroke by Rotarod test, Adhesive Removal test, and Morris Water Maze test. These findings suggest that spontaneous white matter repair occurs after ischemic stroke, while CD11c+ microglia play critical roles in this white matter restorative progress.

Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk.

Osteoarthritis (OA) is a chronic, progressive, severely debilitating, and multifactorial joint disease that is recognized as the most common type of arthritis. During the last decade, it shows an incremental global rise in prevalence and incidence. The interaction between etiologic factors that mediate joint degradation has been explored in numerous studies. However, the underlying processes that induce OA remain obscure, largely due to the variety and complexity of these mechanisms. During synovial joint dysfunction, the osteochondral unit undergoes cellular phenotypic and functional alterations. At the cellular level, the synovial membrane is influenced by cartilage and subchondral bone cleavage fragments and extracellular matrix (ECM) degradation products from apoptotic and necrotic cells. These "foreign bodies" serve as danger-associated molecular patterns (DAMPs) that trigger innate immunity, eliciting and sustaining low-grade inflammation in the synovium. In this review, we explore the cellular and molecular communication networks established between the major joint compartments-the synovial membrane, cartilage, and subchondral bone of normal and OA-affected joints.

Automated non-branching protrusion design with evolutionary algorithm in communication via diffusion

Molecular communication via diffusion enables information transmission between nanomachines in nanonetworking. Although the interconnection of multiple bodies expands their capabilities to a certain extent, it still poses some challenges to improve communication efficiency. The degradation in the molecular reception performance of the receiver over long channels is the one that can be mitigated through availability of protrusions. In this paper, we propose special version of protrusion location optimization extended with non-branching protrusions which consist of multiple interdependent segments. For the given problem, we present novel evolutionary optimization algorithm (i.e. GADP: Genetic Algorithm Distributed Protrusions) to maximize the probability of molecule hit as an objective. The motivation is to utilize the evolving and dynamic nature of evolutionary optimization to handle different scenarios including varying distances between the transmitter and the receiver. The proposed algorithm is subjected to extensive experimental study where it outperforms the existing algorithms from the literature in majority of the cases. Furthermore, we analyse the final versions of protrusions at the end of evolution to reveal their structural and locational properties.

Feedback-Controlled Adaptive Signal Detection Scheme for Diffusion-Based Molecular Communication Systems

This paper proposes a feedback-controlled adaptive method for detecting signals in diffusion-based molecular communication (MC) systems. Signal detection via a receiver nanomachine is a critical challenge for the exchange of information in MC systems. Incorrect estimations or small errors in signal detection can lead to high data detection errors. Existing methods for improving detection performance require high time costs or computational complexity. This paper proposes a simple and practical method that enables receiver nanomachines to automatically estimate signal detection times according to the measured molecular concentrations and weighted feedback errors. The proposed method adjusts the detection time even when the initial parameter values of the system are unknown to the receiver nanomachines. Simulations were performed to evaluate the bit error rate performance of the proposed and existing methods in terms of different data rates, transmission distances, and estimation error lengths under different initial conditions. The simulation results reveal that the implementation of the proposed method is simpler and demonstrates superior performance compared with that of existing methods.

Channel Characterization and Performance of a 3-D Molecular Communication System With Multiple Fully-Absorbing Receivers

Molecular communication (MC) can enable the transfer of information between nanomachines using molecules as the information carrier. In MC systems, multiple receiver nanomachines often co-exist in the same communication channel to serve common or different purposes. However, the analytical channel model for a system with multiple fully absorbing receivers (FARs), which is significantly different from the single FAR system due to the mutual influence of FARs, does not exist in the literature. The analytical channel model is essential in analyzing systems with multiple FARs, including MIMO, SIMO, and cognitive molecular communication systems. In this work, we derive an analytical expression for the hitting probability of a molecule emitted from a point source on each FAR in a diffusion-based MC system with <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$N$ </tex-math></inline-formula> FARs. Using these expressions, we derive the channel model for a SIMO system with a single transmitter and multiple FARs arranged in a uniform circular array (UCA). We then analyze the communication performance of this SIMO system under different cooperative detection schemes and develop several interesting insights.

Health Equity in Sickle Cell Research and Access to Therapy

Health Equity in Sickle Cell Research and Access to Therapy

Deciphering the mechanism of resistance by novel double mutations in pncA in Mycobacterium tuberculosis using protein structural graphs (PSG) and structural bioinformatic approaches

The evolution of MDR and XDR-TB is a growing concern and public health safety threat around the world. Gene mutations are the prime cause of drug resistance in tuberculosis, however the reports of double mutations further aggravated the situation. Despite the large-scale genomic sequencing and identification of novel mutations, structure investigation of the protein is still required to structurally and functionally characterize these novel mutations to design novel drugs for improved clinical outcome. Hence, we used structural bioinformatics approaches i.e. molecular modeling, residues communication and molecular simulation to understand the impact of novel double S59Y-L85P, D86G-V180F and S104G-V130 M mutation on the structure, function of pncA encoded Pyrazinamidase (PZase) and resistance of Pyrazinamide (PZA). Our results revealed that these mutations alter the binding paradigm and destabilize the protein to release the drug. Protein commination network (PCN) revealed variations in the hub residues and sub-networks which consequently alter the internal communication and signaling. The region 1–75 demonstrated higher flexibility in the mutant structures and minimal by the wild type which destabilize of the internally arranged beta-sheets which consequently reduce the binding of PZA and potentially Fe ion in the mutants. Hydrogen bonding analysis further validated the findings. The total binding free energy (ΔG) for each complex i.e. wild type −7.46 kcal/mol, S59Y-L85P −5.21 kcal/mol, S104G-V130 M −5.33 kcal/mol while for the D86G-V180F mutant the TBE was calculated to be −6.26 kcal/mol. This further confirms that these mutations reduce the binding energy of PZA for PZase and causes resistance in the effective therapy for TB. The trajectories motion was also observed to be affected by these mutations. In conclusion, these mutations use destabilizing approach to reduce the binding of PZA and causes resistance. These features can be used to design novel structure-based drugs against Tuberculosis.

Realization of Achromatic and Wide-Field Doublet Metalens in Mid-Infrared Spectra

Metalenses has been proposed to replace bulky and heavy refractive lenses. In the mid-infrared (MIR) range, simultaneous realization of wide-field and achromatic imaging for MIR metalense has so far not been achieved. In this letter, we design and fabricate a MIR metalens that achieves achromatic imaging with a field of view (FOV) of 60° in the wavelength range of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$10~\mu \text{m}$ </tex-math></inline-formula> to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$11~\mu \text{m}$ </tex-math></inline-formula> . Experimental results show that the average focusing efficiencies of the metalens are 20.62% at 0° incident angle and 9.1% at 30° incident angle. This metalens provides potential in many applications, such as molecular fingerprint detection, night vision and free space communication.

Toward Interdisciplinary Synergies in Molecular Communications: Perspectives from Synthetic Biology, Nanotechnology, Communications Engineering and Philosophy of Science.

Within many chemical and biological systems, both synthetic and natural, communication via chemical messengers is widely viewed as a key feature. Often known as molecular communication, such communication has been a concern in the fields of synthetic biologists, nanotechnologists, communications engineers, and philosophers of science. However, interactions between these fields are currently limited. Nevertheless, the fact that the same basic phenomenon is studied by all of these fields raises the question of whether there are unexploited interdisciplinary synergies. In this paper, we summarize the perspectives of each field on molecular communications, highlight potential synergies, discuss ongoing challenges to exploit these synergies, and present future perspectives for interdisciplinary efforts in this area.

Multi-Hop Genetic-Algorithm-Optimized Routing Technique in Diffusion-Based Molecular Communication

Molecular communication (MC) is a modern communication paradigm inspired by biological mechanisms and systems. Due to the short range of molecular diffusion, MC systems necessitate a multi-hop diffusion-based network to transmit information. Finding the optimal routing path is one of the most critical challenges in MC. The main goal is to transfer information through the diffusion of molecules within an optimal state by detecting the shortest route and the proper relays. In this paper, finding the optimal routing path using a genetic algorithm (GA) is investigated in order to find the shortest and the most energy-efficient path. Our model intelligently plans the optimum trajectory between the transmitter (TX) and the receiver (RX) by identifying the appropriate relays both locally and globally. Our GA implementation uses a variable-length chromosome encoding to obtain the optimal path by selecting an appropriate fitness function. We also examine and compare the performance of the proposed algorithm with Dijkstra’s algorithm (DA), which is one of the deterministic algorithms. Finally, various simulations for different sizes of MC networks are performed to verify the accuracy of the proposed method. Our simulation results demonstrate that the presented GA offers an accurate routing path within an excellent time, even in large-sized environments.

Performance analysis of nanosystem based on cooperative relay for nanonetworks

&lt;abstract&gt; &lt;p&gt;Recent nanomedical applications, particularly targeted drug delivery system (TDDS) scenarios, have made use of molecular communications via diffusion (MCvD) based on nanosystems. In order to improve the performance of such nanosystems, nanonetworks-based molecular communication is investigated. Employing a nanorelay approach and cooperative molecular communications, we provide a method for optimizing the performance of the nanosystem while taking blood flow effects into consideration in terms of drift velocity. Unlike the earlier studies, the position of the nanorelay and the allocated amount of molecular drugs will be optimized. We provide closed-form expressions for molecular channel capacity and the error probability of a molecular frame. According to the simulation results, it is possible to significantly reduce error probability of a molecular frame and thus increase channel capacity by optimizing the drift velocity, detection threshold and the location of the nanorelay within the proposed nanosystem.&lt;/p&gt; &lt;/abstract&gt;

A Study of Chemical Reactions in Point-to-Point Diffusion-Based Molecular Communication

The differential equations describing reaction-diffusion systems in molecular communication are non-linear and do not admit closed-form solutions in general. Consequently, characterizing optimal modulation and coding strategies is a key challenge in molecular communication. In this paper, we consider a concrete example and illustrate the application of tools from real and complex analysis to study this difficult problem. We show that the optimal release pattern is a finite sum of Dirac’s delta functions in our working example. Simulation results validate the discrete nature of the optimal release pattern. We also provide an upper bound on the numbers of delta functions under some assumptions.

Convolutional Codec Implemented by Genetic Circuits for Molecular Communication.

Molecular communication (MC), which transmits information through molecules, has emerged as a promising technique to enable communication links between nanomachines. To establish information transmission using molecules, synthetic biology through genetic circuits techniques can be utilized to construct biological components. Recent efforts on genetic circuits have produced many exciting MC systems and generated substantial insights. With basic gene regulatory modules and motifs, researchers are now constructing artificial networks with novel functions that will serve as building blocks in the MC system. In this paper, we investigate the design of genetic circuits to implement the convolutional codec in a diffusion-based MC channel with the concentration shift keying (CSK) transmission scheme. At the receiver, a majority-logic decoder is applied to decode the received symbols. These functions are completely realized in the field of biochemistry through the activation and inhibition of genes and biochemical reactions, rather than through classical electrical circuits. Biochemical simulations are used to verify the feasibility of the system and analyze the impairments caused by diffusion noise and chemical reaction noise of genetic circuits.

Abnormality Detection and Localization Schemes Using Molecular Communication Systems: A Survey

Abnormality detection and localization (ADL) have been studied widely in wireless sensor networks (WSNs) literature, where the sensors use electromagnetic waves for communication. Molecular communication (MC) has been introduced as an alternative approach for ADL in particular areas such as healthcare, being able to tackle the shortcomings of conventional WSNs, such as invasiveness, bio-incompatibility, and high energy consumption. In this paper, we introduce a general framework for MC-based ADL, which consists of multiple tiers for sensing the abnormality and communication between different agents, including the sensors, the fusion center (FC), the gateway (GW), and the external node (e.g., a local cloud), and describe each tier and the agents in this framework. We classify and explain different abnormality recognition methods, the functional units of the sensors, and different sensor features. Further, we describe different types of interfaces required for converting the internal and external signals at the FC and GW. Moreover, we present a unified channel model for the sensing and communication links. We categorize the MC-based abnormality detection schemes based on the sensor mobility, cooperative detection, and cooperative sensing/activation. We also classify the localization approaches based on the sensor mobility and propulsion mechanisms and present a general framework for the externally-controllable localization systems. Finally, we present some challenges and future research directions to realize and develop MC-based systems for ADL. The important challenges in the MC-based systems lie in four main directions as implementation, system design, modeling, and methods, which need considerable attention from multidisciplinary perspectives.

Open multi-organ communication device for easy interrogation of tissue slices.

Here, we have developed an open multi-organ communication device that facilitates cellular and molecular communication between ex vivo organ slices. Measuring communication between organs is vital for understanding the mechanisms of health regulation yet remains difficult with current technology. Communication between organs along the gut-brain-immune axis is a key regulator of gut homeostasis. As a novel application of the device, we have used tissue slices from the Peyer's patch (PP) and mesenteric lymph node (MLN) due to their importance in gut immunity; however, any organ slices could be used here. The device was designed and fabricated using a combination of 3D printed molds for polydimethylsiloxane (PDMS) soft lithography, PDMS membranes, and track-etch porous membranes. To validate cellular and protein transfer between organs on-chip, we used fluorescence microscopy to quantitate movement of fluorescent proteins and cells from the PP to the MLN, replicating the initial response to immune stimuli in the gut. IFN-γ secretion during perfusion from a naïve vs. inflamed PP to a healthy MLN was quantitated to demonstrate soluble signaling molecules are moving on-chip. Finally, transient catecholamine release was measured during perfusion from PP to MLN using fast-scan cyclic voltammetry at carbon-fiber microelectrodes to demonstrate a novel application of the device for real-time sensing during communication. Overall, we show an open-well multi-organ device capable of facilitating transfer of soluble factors and cells with the added benefit of being available for external analysis techniques like electrochemical sensing which will advance abilities to probe communication in real-time across multiple organs ex vivo.

High-Speed Molecular Communication in Vacuum

High-Speed Molecular Communication in Vacuum

TALKIEN: crossTALK IntEraction Network. A web-based tool for deciphering molecular communication through ligand-receptor interactions.

Molecular crosstalk, the dialogue between different cell types, is attracting more attention in cancer research. On the one hand, the communication between tumor and non-tumor cells in the microenvironment or between different tumor clones has influential consequences for the progression and spread of tumors and response to treatment. On the other hand, novel techniques such as single-cell sequencing or spatial transcriptomics provide detailed information that needs to be interpreted. TALKIEN: crossTALK IntEraction Network is a simple and intuitive online R/shiny application to visualize molecular crosstalk information through the construction and analysis of a protein-protein interaction network. Taking two or more lists of genes or proteins as input, which are representative of cell lineages, TALKIEN extracts information about ligand-receptor interactions, builds a network and analyzes it using systems biology techniques such as centrality measures and component analysis, among others. Moreover, it expands the network displaying pathways downstream receptors. The application allows users to select different graphical layouts, performs functional analysis and gives information about drugs targeting receptors. In conclusion, TALKIEN allows users to detect ligand-receptor interactions generating new in silico predictions of cell-cell communication thus providing a translational rationale for future experiments. It is freely available at https://www.odap-ico.org/talkien.

Internet of Bio Nano Things-based FRET nanocommunications for eHealth.

The integration of the Internet of Bio Nano Things (IoBNT) with artificial intelligence (AI) and molecular communications technology is now required to achieve eHealth, specifically in the targeted drug delivery system (TDDS). In this work, we investigate an analytical framework for IoBNT with Forster resonance energy transfer (FRET) nanocommunication to enable intelligent bio nano thing (BNT) machine to accurately deliver therapeutic drug to the diseased cells. The FRET nanocommunication is accomplished by using the well-known pair of fluorescent proteins, EYFP and ECFP. Furthermore, the proposed IoBNT monitors drug transmission by using the quenching process in order to reduce side effects in healthy cells. We investigate the IoBNT framework by driving diffusional rate models in the presence of a quenching process. We evaluate the performance of the proposed framework in terms of the energy transfer efficiency, diffusion-controlled rate and drug loss rate. According to the simulation results, the proposed IoBNT with the intelligent bio nano thing for monitoring the quenching process can significantly achieve high energy transfer efficiency and low drug delivery loss rate, i.e., accurately delivering the desired therapeutic drugs to the diseased cell.

Dual Ionic Transport Using Ca2+and Na2+Signaling for Molecular Communication Systems

Astrocytes have the ability to modulate neuronal communication by regulating various levels of ionic concentrations. The development of models for molecular communication ought to investigate the utilisation of various ionic transportation mechanisms, with the aim of enhancing performance and biocompatibility, thereby facilitating co-existence within cellular tissues. In this study, we suggest the utilisation of both Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> and Na <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> ions to investigate the non-linearities of propagation in cellular tissues for MC. In this study, we also investigated the impact of various ionic transport mechanisms, including the sodium-calcium exchanger, sodium-potassium pump, and calcium pump, to assess their impact on the intracellular propagation of Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> . We analysed four metrics, namely channel capacity, bit error rate (BER), communication gain, and signal-to-noise ratio, to evaluate the effects of these structures.