Propagation Modeling and Analysis of Molecular Motors in Molecular Communication.

Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming.

Pharmacokinetic Modeling and Biodistribution Estimation Through the Molecular Communication Paradigm.

Targeted drug delivery systems (TDDSs) are therapeutic methods based on the injection and delivery of drug-loaded particles. The engineering of TDDSs must take into account both the therapeutic effects of the drug at the target delivery location and the toxicity of the drug while it accumulates in other regions of the body. These characteristics are directly related to how the drug-loaded particles distribute within the body, i.e., biodistribution, as a consequence of the processes involved in the particle propagation, i.e., pharmacokinetics. In this paper, the pharmacokinetics of TDDSs is analytically modeled through the abstraction of molecular communication, a novel paradigm in communication theory. Not only is the particle advection and diffusion, considered in our previous study, included in this model, but also are other physicochemical processes in the particle propagation, such as absorption, reaction, and adhesion. In addition, the proposed model includes the impact of cardiovascular diseases, such as arteriosclerosis and tumor-induced blood vessel leakage. Based on this model, the biodistribution at the delivery location is estimated through communication engineering metrics, such as channel delay and path loss, together with the drug accumulation in the rest of the body. The proposed pharmacokinetic model is validated against multiphysics finite-element simulations, and numerical results are provided for the biodistribution estimation in different scenarios. Finally, based on the proposed model, a procedure to optimize the drug injection rate is proposed to achieve a desired drug delivery rate. The outcome of this study is a multiscale physics-based analytical pharmacokinetic model.

Molecular Communication Modeling of Antibody-Mediated Drug Delivery Systems.

Antibody-mediated Drug Delivery Systems (ADDS) are emerging as one of the most encouraging therapeutic solutions for treating several diseases such as human cancers. ADDS use small molecules (antibodies) that propagate in the body and bind selectively to their corresponding receptors (antigens) expressed at the surface of the diseased cells. In this paper, the Molecular Communication (MC) paradigm, where information is conveyed through the concentration of molecules, is advocated for the engineering of ADDS and modeling their complex behavior, to provide a realistic model without the over-complication of system biology models, and the limitations of experimental approaches. The peculiarities of antibodies, including their anisotropic transport and complex electrochemical structure, are taken into account to develop an analytical model of the ADDS transport and antigen-binding kinetics. The end-to-end response of ADDS, from the drug injection to the drug absorption, is mathematically derived based on the geometry of the antibody molecule, the electrochemical structure of the antibody-antigen complex, and the physiology of the patient. The accuracy of the MC model is validated by finite-element (COMSOL) simulations. The implications of the complex interplay between the transport and kinetics parameters on the performance of ADDS are effectively captured by the proposed MC model. The MC model of ADDS will enable the discovery and optimization of drugs in a versatile, cost-efficient, and reliable manner.

An intra-body molecular communication networks framework for continuous health monitoring and diagnosis.

Intra-body communication networks are designed to interconnect nano- or micro-sized sensors located inside the body for health monitoring and drug delivery. The most promising solutions are made of implanted nanosensors to timely monitor the body for the presence of specific diseases and pronounce a diagnosis without the intervention of a physician. In this manner, several deadly health conditions such as heart attacks are avoided through the early in vivo detection of their biomarkers. In reality, nanosensors are challenged by the individual specificities, molecular noise, limited durability, and low energy resources. In this paper, a framework is proposed for estimating and detecting diseases and localizing the nanosensors. This framework is based on molecular communication, a novel communication paradigm where information is conveyed through molecules. Through the case study of the shedding of endothelial cells as an early biomarker for heart attack, the intra-body molecular communication networks framework is shown to resolve major issues with in vivo nanosensors and lay the foundations of low-complexity biomedical signal processing algorithms for continuous disease monitoring and diagnosis.

Antibody-based molecular communication for targeted drug delivery systems.

Antibody-based drug delivery systems (ADDS) are established as the most promising therapeutic methods for the treatment of human cancers and other diseases. ADDS are composed of small molecules (antibodies) that selectively bind to receptors (antigens) expressed by the diseased cells. In this paper, the Molecular Communication (MC) paradigm, where the delivery of molecules is abstracted as the delivery of information, is extended to be applied to the design and engineering of ADDS. The authors have previously developed a straightforward framework for the modeling of Particulate Drug Delivery Systems (PDDS) using nano-sized molecules. Here, the specificities of antibody molecules are taken into account to provide an analytical model of ADDS transport. The inputs of the MC model of PDDS are the geometric properties of the antibodies and the topology of the blood vessels where they are propagated. Numerical results show that the analytical MC model is in good agreement with finite-element simulations, and that the anisotropy is an important factor influencing ADDS.

A Molecular Communication System Model for Particulate Drug Delivery Systems.

The goal of a drug delivery system (DDS) is to convey a drug where the medication is needed, while, at the same time, preventing the drug from affecting other healthy parts of the body. Drugs composed of micro- or nano-sized particles (particulate DDS) that are able to cross barriers which prevent large particles from escaping the bloodstream are used in the most advanced solutions. Molecular communication (MC) is used as an abstraction of the propagation of drug particles in the body. MC is a new paradigm in communication research where the exchange of information is achieved through the propagation of molecules. Here, the transmitter is the drug injection, the receiver is the drug delivery, and the channel is realized by the transport of drug particles, thus enabling the analysis and design of a particulate DDS using communication tools. This is achieved by modeling the MC channel as two separate contributions, namely, the cardiovascular network model and the drug propagation network. The cardiovascular network model allows to analytically compute the blood velocity profile in every location of the cardiovascular system given the flow input by the heart. The drug propagation network model allows the analytical expression of the drug delivery rate at the targeted site given the drug injection rate. Numerical results are also presented to assess the flexibility and accuracy of the developed model. The study of novel optimization techniques for a more effective and less invasive drug delivery will be aided by this model, while paving the way for novel communication techniques for Intrabody communication networks.