Practical Transmitters for Molecular Communication: Functionalized Nanodevices Employing Cooperative Transmembrane Transport Proteins

TL;DR

The work addresses the practical realization of molecular communication transmitters by proposing vesicular nanodevices (NDs) that use two cooperating transmembrane protein modules to optically control signaling-molecule release. It develops a rigorous system model with single-vesicle (SVS) and multi-vesicle (MVS) configurations, derives exact and closed-form analytical solutions for ion and substrate fluxes, and incorporates buffering and parameter randomness to reflect realistic environments. The authors validate their analytical results against a numerical solver, demonstrating how buffering and stochastic vesicle parameters influence release kinetics and overall TX behavior, and show that MVS cannot be accurately represented by a single SVS with mean parameters in the presence of transport activity. The findings yield design guidelines on the ratio of energizing pumps to release co-transporters and buffer strength, clarifying how to achieve reliable, externally controllable MC transmission and providing a framework for in silico optimization and experimental realization of ND-based MC transmitters.

Abstract

This paper introduces a novel optically controllable molecular communication (MC) transmitter (TX) design based on vesicular nanodevices (NDs). The NDs are functionalized for the controlled release of signaling molecules (SMs) via transmembrane proteins. The proposed design contributes to overcoming the current barrier between MC theory and practical implementation, as all components of the system are chemically realizable. The NDs possess an optical-to-chemical conversion capability, therefore, the proposed NDs can be employed as externally controllable TXs in various MC systems. The proposed ND design comprises two cooperating modules, namely an energizing module and a release module, and, depending on the specific choices for the modules, allows for the release of different types of SMs. After introducing the general system model for the proposed realistic TX design, we provide a detailed mathematical analysis of a specific TX realization. In particular, we derive both an exact and a closed-form approximate analytical solution for the concentration of the released SMs and validate our results by comparison with a numerical solution. Moreover, we model the impact of a buffering medium, which is typically present in liquid environments, e.g., in experimental settings or in in-body applications. This allows the evaluation of the feasibility of our proposed TX design in practical chemical implementations. We consider various forms of parameter randomness occurring during vesicle synthesis, i.e., deviations which are unavoidable during experiments. We show that considering random distributions of the parameter values, such as the ND size, the number of incorporated proteins on the vesicle surface, and the vesicle membrane permeability, is crucial for an adequate kinetic analysis of the system.

Figures (13)

• Figure 1: General system model for the proposed ND-based TX. (a): Experimental set up of an MVS where $n_{\mathrm{ves}}$ND are contained in volume $\mathcal{V}_{\mathrm{out,tot}}$. (b): Detailed view of SVS $m \in \{1,2,\ldots,n_{\mathrm{ves}}\}$ in the MVS. Variables $i^{\mathrm{I}}_{\mathrm{E},m}$, $i^{\mathrm{I}}_{\mathrm{L},m}$, $i^{\mathrm{I}}_{\mathrm{R},m}$, and $i^{\mathrm{S}}_{\mathrm{R},m}$ denote the flux of ion $\mathrm{I}$ caused by the energizing module, the leakage flux of $\mathrm{I}$, and the flux of $\mathrm{I}$ and substrate $\mathrm{S}$ caused by the release module in vesicle $m$, respectively. The possible flux directions between the intravesicular volume, $\mathcal{V}_{\mathrm{in}}$, and the extravesicular volume, $\mathcal{V}_{\mathrm{out}}$, are indicated by arrows. The complex that the buffering ligand $\mathrm{B}$ may form with $\mathrm{I}$ is also depicted (complex of green and grey dots). The energizing and release module in each vesicle consists of multiple transmembrane transport proteins. Examples of suitable proteins and their transported cargo molecules are shown on the right-hand side. Abbreviations: AA = amino acid, NT = neurotransmitter. Created with BioRender.com.
• Figure 2: (a): A regular illumination cycle for an ND with ${n_{\mathrm{P}} = 3}$ and ${n_{\mathrm{Sym}} = 2}$ comprising four different cycle phases. The times ${t^{(1)}_{i}}$, ${t^{(2)}_{i}}$, ${t^{(3)}_{i}}$, and ${t^{(4)}_{i}}$ mark the transitions between two cycle phases. Here, ${C^{\mathrm{H^{+}}}_{\xi}}$ indicates the symport threshold concentration. (b): A cycle without symporter activity. (c): Two subsequent cycles in between which the symport does not end. Parts of the image were created with BioRender.com.
• Figure 3: Visualization of the considered random processes and distributions underlying the vesicle production process and influencing the vesicle diameter (left), the number of pumps and symporters per vesicle (center), and the membrane permeability to $\mathrm{H^{+}}$ (right). Created with BioRender.com.
• Figure 4: Intravesicular $\mathrm{H^{+}}$ concentration, $C^{\mathrm{H^{+}}}_{\mathrm{in}}(t)$, (bottom) for one illumination period without release module, i.e., $n_{\mathrm{Sym}} = 0$, and for varying buffer molarities $C_{0}$. Results obtained with FDM (blue), the exact analytical solution \ref{['eq:chin_aci']} (green), and the approximate analytical solution \ref{['eq:ana_chin']} (orange) are shown as a function of time $t$. The light signal $l(t)$ (red) is shown on the top. Shaded gray areas indicate times during which $l(t) = 1$. The black line shows the $\mathrm{H^{+}}$ concentration, $C^{\mathrm{H^{+}}}_{\mathrm{in,eq}}$, where in- and outflux to/from the vesicle are in equilibrium while $l(t) = 1$.
• Figure 5: Intravesicular $\mathrm{H^{+}}$ concentration (middle panel) and extravesicular $\mathrm{S}$ concentration (bottom panel) for different cycle types (a), (b), and (c) and solution approaches. The active system components during each cycle phase are shown on top (green: proton pumps, orange: symporters, blue: leakage) and dashed lines indicate cycle phase limits. The intravesicular $\mathrm{H^{+}}$ concentration required for symport activation, $C^{\mathrm{H^{+}}}_{\xi}$, is shown by the horizontal black line in the middle panel.

Theorems & Definitions (6)

• proof : Proposition 1
• proof
• Theorem 1
• proof
• Theorem 2
• proof