Performance Analysis and ISI Mitigation with Imperfect Transmitter in Molecular Communication.

In molecular communication (MC), molecules are released from the transmitter to convey information. This paper considers a realistic molecule shift keying (MoSK) scenario with two species of molecule in two reservoirs, where the molecules are harvested from the environment and placed into different reservoirs, which are purified by exchanging molecules between the reservoirs. This process consumes energy, and for a reasonable energy cost, the reservoirs cannot be pure; thus, our MoSK transmitter is imperfect, releasing mixtures of both molecules for every symbol, resulting in inter-symbol interference (ISI). To mitigate ISI, the properties of the receiver are analyzed and a detection method based on the ratio of different molecules is proposed. Theoretical and simulation results are provided, showing that with the increase of energy cost, the system achieves better performance. The good performance of the proposed detection scheme is also demonstrated.

A transistor model for the cystic fibrosis transmembrane conductance regulator.

In this paper we present a transistor circuit model for cystic fibrosis transmembrane conductance regulator (CFTR) that seeks to map the functional form of CFTR both in wild type and mutants. The circuit architecture is configured so that the function, and as much as possible the form, faithfully represents what is known about CFTR from cryo-electron microscopy and molecular dynamics. The model is a mixed analog-digital topology with an AND gate receiving the input from two separate ATP-nucleotide-binding domain binding events. The analog portion of the circuit takes the output from the AND gate as its input. The input to the circuit model and its noise characteristics are extracted from single-channel patch-clamp experiments. The chloride current predicted by the model is then compared with single-channel patch-clamp recordings for wild-type CFTR. We also consider the patch-clamp recordings from CFTR with a G551D point mutation, a clinically relevant mutant that is responsive to therapeutic management. Our circuit model approach enables bioengineering approaches to CFTR and allows biophysicists to use efficient circuit simulation tools to analyze its behavior.

Explicitly Solvable Continuous-time Inference for Partially Observed Markov Processes.

Many natural and engineered systems can be modeled as discrete state Markov processes. Often, only a subset of states are directly observable. Inferring the conditional probability that a system occupies a particular hidden state, given the partial observation, is a problem with broad application. In this paper, we introduce a continuous-time formulation of the sum-product algorithm, which is a well-known discrete-time method for finding the hidden states' conditional probabilities, given a set of finite, discrete-time observations. From our new formulation, we can explicitly solve for the conditional probability of occupying any state, given the transition rates and observations within a finite time window. We apply our algorithm to a realistic model of the cystic fibrosis transmembrane conductance regulator (CFTR) protein for exact inference of the conditional occupancy probability, given a finite time series of partial observations.

Selectivity of Protein Interactions Stimulated by Terahertz Signals.

It has been established that Terahertz (THz) band signals can interact with biomolecules through resonant modes. Specifically, of interest here, protein activation. Our research goal is to show how directing the mechanical signaling inside protein molecules using THz signals can control changes in their structure and activate associated biochemical and biomechanical events. To establish that, we formulate a selectivity metric that quantifies the system performance and captures the capability of the nanoantenna to induce a conformational change in the desired protein molecule/population. The metric provides a score between -1 and 1 that indicates the degree of control we have over the system to achieve targeted protein interactions. To develop the selectivity measure, we first use the Langevin stochastic equation driven by an external force to model the protein behavior. We then determine the probability of protein folding by computing the steady-state energy of the driven protein and then generalize our model to account for protein populations. Our numerical analysis results indicate that a maximum selectivity score is attained when only the targeted population experiences a folding behavior due to the impinging THz signal. From the achieved selectivity values, we conclude that the system response not only depends on the resonant frequency but also on the system controlling parameters namely, the nanoantenna force, the damping constant, and the abundance of each protein population. Based on the selectivity metric, the nanoantenna must be tuned to a frequency that is not necessarily the resonant frequency of the protein. The presented work sheds light on the potential associated with the electromagnetic-based control of protein networks, which could lead to a plethora of applications in the medical field ranging from bio-sensing to targeted therapy.

Permissive and nonpermissive channel closings in CFTR revealed by a factor graph inference algorithm.

The closing of the gated ion channel in the cystic fibrosis transmembrane conductance regulator can be categorized as nonpermissive to reopening, which involves the unbinding of ADP or ATP, or permissive, which does not. Identifying the type of closing is of interest as interactions with nucleotides can be affected in mutants or by introducing agonists. However, all closings are electrically silent and difficult to differentiate. For single-channel patch-clamp traces, we show that the type of the closing can be accurately determined by an inference algorithm implemented on a factor graph, which we demonstrate using both simulated and lab-obtained patch-clamp traces.

Cheater suppression and stochastic clearance through quorum sensing.

The evolutionary consequences of quorum sensing in regulating bacterial cooperation are not fully understood. In this study, we reveal unexpected effects of regulating public good production through quorum sensing on bacterial population dynamics, showing that quorum sensing can be a collectively harmful alternative to unregulated production. We analyze a birth-death model of bacterial population dynamics accounting for public good production and the presence of non-producing cheaters. Our model demonstrates that when demographic noise is a factor, the consequences of controlling public good production according to quorum sensing depend on the cost of public good production and the growth rate of populations in the absence of public goods. When public good production is inexpensive, quorum sensing is a destructive alternative to unconditional production, in terms of the mean population extinction time. When costs are higher, quorum sensing becomes a constructive strategy for the producing strain, both stabilizing cooperation and decreasing the risk of population extinction.

Minimal informational requirements for fitness.

The existing concept of the "fitness value of information" provides a theoretical upper bound on the fitness advantage of using information concerning a fluctuating environment. Using concepts from rate-distortion theory, we develop a theoretical framework to answer a different pair of questions: What is the minimal amount of information needed for a population to achieve a certain growth rate? What is the minimal amount of information gain needed for one subpopulation to achieve a certain average selection coefficient over another? We introduce a correspondence between fitness and distortion and solve for the rate-distortion functions of several systems using analytical and numerical methods. Because accurate information processing is energetically costly, our approach provides a theoretical basis for understanding evolutionary "design principles" underlying information-cost trade-offs.

Information Rates of Controlled Protein Interactions Using Terahertz Communication.

In this work, we present a paradigm bridging electromagnetic (EM) and molecular communication through a stimuli-responsive intra-body model. It has been established that protein molecules, which play a key role in governing cell behavior, can be selectively stimulated using Terahertz (THz) band frequencies. By triggering protein vibrational modes using THz waves, we induce changes in protein conformation, resulting in the activation of a controlled cascade of biochemical and biomechanical events. To analyze such an interaction, we formulate a communication system composed of a nanoantenna transmitter and a protein receiver. We adopt a Markov chain model to account for protein stochasticity with transition rates governed by the nanoantenna force. Both two-state and multi-state protein models are presented to depict different biological configurations. Closed form expressions for the mutual information of each scenario is derived and maximized to find the capacity between the input nanoantenna force and the protein state. The results we obtain indicate that controlled protein signaling provides a communication platform for information transmission between the nanoantenna and the protein with a clear physical significance. The analysis reported in this work should further research into the EM-based control of protein networks.

Fitness value of information with delayed phenotype switching: Optimal performance with imperfect sensing.

The ability of organisms to accurately sense their environment and respond accordingly is critical for evolutionary success. However, exactly how the sensory ability influences fitness is a topic of active research, while the necessity of a time delay between when unreliable environmental cues are sensed and when organisms can mount a response has yet to be explored at any length. Accounting for this delay in phenotype response in models of population growth, we find that a critical error probability can exist under certain environmental conditions: An organism with a sensory system with any error probability less than the critical value can achieve the same long-term growth rate as an organism with a perfect sensing system. We also observe a tradeoff between the evolutionary value of sensory information and robustness to error, mediated by the rate at which the phenotype distribution relaxes to steady state. The existence of the critical error probability could have several important evolutionary consequences, primarily that sensory systems operating at the nonzero critical error probability may be evolutionarily optimal.

Communication in Plants: Comparison of Multiple Action Potential and Mechanosensitive Signals With Experiments.

Both action potentials and mechanosensitive signalling are an important communication mechanisms in plants. Considering an information-theoretic framework, this paper explores the effective range of multiple action potentials for a long chain of cells (i.e., up to 100) in different configurations, and introduces the study of multiple mechanosensitive activation signals (generated due to a mechanical stimulus) in plants. For both these signals, we find that the mutual information per cell and information propagation speed tends to increase up to a certain number of receiver cells. However, as the number of cells increase beyond 10 to 12, the mutual information per cell starts to decrease. To validate our model and results, we include an experimental verification of the theoretical model, using a PhytlSigns biosignal amplifier, allowing us to measure the magnitude of the voltage associated with the multiple AP's and mechanosensitive activation signals induced by different stimulus in plants. Experimental data is used to calculate the mutual information and information propagation speed, which is compared with corresponding numerical results. Since these signals are used for a variety of important tasks within the plant, understanding them may lead to new bioengineering methods for plants.

Communication and Information Theory of Single Action Potential Signals in Plants.

Many plants, such as Mimosa pudica (the "sensitive plant"), employ electrochemical signals known as action potentials (APs) for rapid intercellular communication. In this paper, we consider a reaction-diffusion model of individual AP signals to analyze APs from a communication- and information-theoretic perspective. We use concepts from molecular communication to explain the underlying process of information transfer in a plant for a single AP pulse that is shared with one or more receiver cells. We also use the chemical Langevin equation to accommodate the deterministic as well as stochastic component of the system. Finally, we present an information-theoretic analysis of single action potentials, obtaining achievable information rates for these signals. We show that, in general, the presence of an AP signal can increase the mutual information and information propagation speed among neighboring cells with receivers in different settings.

Distortion Distribution of Neural Spike Train Sequence Matching With Optogenetics.

OBJECTIVE: This paper uses a simple optogenetic model to compare the timing distortion between a randomly-generated target spike sequence and an externally-stimulated neuron spike sequence. Optogenetics is an emerging field of neuroscience where neurons are genetically modified to express light-sensitive receptors that enable external control when the neurons fire. METHODS: Two different measures are studied to determine the timing distortion. The first measure is the delay in externally-stimulated spikes. The second measure is the root-mean-square-error between the filtered outputs of the target and stimulated spike sequences. RESULTS: The mean and the distribution of the distortion are derived in closed form when the target sequence generation rate is sufficiently low. The derived results are verified with simulations. CONCLUSION: The proposed model and distortion measures can be used to measure the deviation between neuron spike sequences that are prescribed and what can be achieved via external stimulation. SIGNIFICANCE: Given the prominence of neuronal signaling within the brain and throughout the body, optogenetics has significant potential to improve the understanding of the nervous system and to develop treatments for neurological diseases. This work is a step towards an analytical model to predict whether different spike trains were observed from the same external stimulus, and the broader goal of understanding the quantity and reliability of information that can be carried by neurons.

Symbol interval optimization for molecular communication with drift.

In this paper, we propose a symbol interval optimization algorithm in molecular communication with drift. Proper symbol intervals are important in practical communication systems since information needs to be sent as fast as possible with low error rates. There is a trade-off, however, between symbol intervals and inter-symbol interference (ISI) from Brownian motion. Thus, we find proper symbol interval values considering the ISI inside two kinds of blood vessels, and also suggest no ISI system for strong drift models. Finally, an isomer-based molecule shift keying (IMoSK) is applied to calculate achievable data transmission rates (achievable rates, hereafter). Normalized achievable rates are also obtained and compared in one-symbol ISI and no ISI systems.

Tabletop molecular communication: text messages through chemical signals.

In this work, we describe the first modular, and programmable platform capable of transmitting a text message using chemical signalling - a method also known as molecular communication. This form of communication is attractive for applications where conventional wireless systems perform poorly, from nanotechnology to urban health monitoring. Using examples, we demonstrate the use of our platform as a testbed for molecular communication, and illustrate the features of these communication systems using experiments. By providing a simple and inexpensive means of performing experiments, our system fills an important gap in the molecular communication literature, where much current work is done in simulation with simplified system models. A key finding in this paper is that these systems are often nonlinear in practice, whereas current simulations and analysis often assume that the system is linear. However, as we show in this work, despite the nonlinearity, reliable communication is still possible. Furthermore, this work motivates future studies on more realistic modelling, analysis, and design of theoretical models and algorithms for these systems.

Molecular communication using Brownian motion with drift.

Inspired by biological communication systems, molecular communication has been proposed as a viable scheme to communicate between nano-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. We analyze the mutual information between transmitter and the receiver when information is encoded in the time of release of the molecule. Simplifying assumptions are required 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.

On-chip molecular communication: analysis and design.

We consider a confined space molecular communication system, where molecules or information carrying particles are used to transfer information on a microfluidic chip. Considering that information-carrying particles can follow two main propagation schemes: passive transport, and active transport, it is not clear which achieves a better information transmission rate. Motivated by this problem, we compare and analyze both propagation schemes by deriving a set of analytical and mathematical tools to measure the achievable information rates of the on-chip molecular communication systems employing passive to active transport. We also use this toolbox 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 is examined under both propagation schemes, and a guidepost to design an optimal molecular communication setup and protocol is presented.