Molecular communication is an emerging communication paradigm for biological nanomachines. It allows biological nanomachines to communicate through exchanging molecules in an aqueous environment and to perform collaborative tasks through integrating functionalities of individual biological nanomachines. This paper develops the layered architecture of molecular communication and describes research issues that molecular communication faces at each layer of the architecture. Specifically, this paper applies a layered architecture approach, traditionally used in communication networks, to molecular communication, decomposes complex molecular communication functionality into a set of manageable layers, identifies basic functionalities of each layer, and develops a descriptive model consisting of key components of the layer for each layer. This paper also discusses open research issues that need to be addressed at each layer. In addition, this paper provides an example design of targeted drug delivery, a nanomedical application, to illustrate how the layered architecture helps design an application of molecular communication. The primary contribution of this paper is to provide an in-depth architectural view of molecular communication. Establishing a layered architecture of molecular communication helps organize various research issues and design concerns into layers that are relatively independent of each other, and thus accelerates research in each layer and facilitates the design and development of applications of molecular communication.

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In molecular communication, a group of biological nanomachines communicates through exchanging molecules and collectively performs application dependent tasks. An open research issue in molecular communication is to establish interfaces to interconnect the molecular communication environment (e.g., inside the human body) and its external environment (e.g., outside the human body). Such interfaces allow conventional devices in the external environment to control the location and timing of molecular communication processes in the molecular communication environment and expand the capability of molecular communication.In this paper, we first describe an architecture of externally controllable molecular communication and introduce two types of interfaces for biological nanomachines; bio-nanomachine to bio-nanomachine interfaces (BNIs) for bio-nanomachines to interact with other biological nanomachines in the molecular communication environment, and inmessaging and outmessaging interfaces (IMIs and OMIs) for bio-nanomachines to interact with devices in the external environment. We then describe a proofof-concept design and wet laboratory implementation of the IMI and OMI, using biological cells. We further demonstrate, through mathematical modeling and numerical experiments, how an architecture of externally controllable molecular communication with BNIs and IMIs/OMIs may apply to pattern formation, a promising nanomedical application of molecular communication.

This paper describes a mobile bionanosensor network designed for target tracking. The mobile bionanosensor network is composed of bacterium-based autonomous biosensors that coordinate their movement through the use of two types of signaling molecules, repellents and attractants. In search of a target, the bacterium-based autonomous biosensors release repellents to quickly spread over the environment, while, upon detecting a target, they release attractants to recruit other biosensors in the environment toward the location around the target. A mobility model of bacterium-based autonomous biosensors is first developed based on the rotational diffusion model of bacterial chemotaxis, and from this their collective movement to track a moving target is demonstrated. In simulation experiments, the mobile bionanosensor network is evaluated based on the mean tracking time. Simulation results show a set of parameter values that can optimize the mean tracking time, providing an insight into how bacterium-based autonomous biosensors may be designed and engineered for target tracking.