Communication Theoretical Foundation of Wireless Nanonetworks

The extracellular vesicles participate in intercellular signalling and are relevant entities to both physiologic and pathologic prosecesses. Novel drug delivery systems may utilise extracellular vesicles as vehicles to carry active biomolecules toward target cells. The CIRCLE project is centered around a computational methodology which theoretically quantifies and analyses the transport of extracellular vesicles in the cardiac tissue for the sake of delivery of therapeutic agents. The initial models have been developed and cover the aspects of the extracellular release from cells, both non-stimulated and stimulated, propagation through the cardiovascular networks and the cardiac extracellular matrix, and the uptake by recipient cells. We have investigated the release of extracellular vesicles from induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes. Our developed models help to get an understanding of the extracellular vesicle dynamics, including the time needed for their secretion and release, as well as the critical components in the biosystem which impact the successful transport of the extracellular vesicles. Our results, reveal that the diffusivity constant, volume fraction and tortuosity of the matrix largely affect transport. An important finding is that ligand-receptor interactions at the target cells may lead to more internalised extracellular vesicles compared to other internalisation mechanisms, for example, clathrin-mediated endocytosis, despite the slow internalisation process at target cells. The research performed so far in CIRLCE has led to new knowledge with which novel research directions emerge. Our next steps are towards the development of an advanced computer model for optimising and evaluating myocardial repair therapy based on extracellular vesicles. Specifically, we will investigate the microRNA-based therapy for the treatment of acute myocardial infarctions in selected patients and evaluate its efficacy prior to administering the therapy. The new computer model will synergise physiology-based modelling with experimental data and artificial intelligence techniques. A foundation will be set in porcine models and subsequently translated into the design of an early feasibility study using patient data.

Intra-body wireless sensor and actuator communication networks are necessary to provide solutions for implantable micro-devices to enable diagnostics, monitoring, and therapy. Current technology has significant drawbacks since presently available deep, bio-compatible implantation systems with life long operation are too poor and slow to support comprehensive diagnosis and therapies. Synthetic biology is an emerging scientific field with major disruptive potentials, and can manipulate cells using nanoscale devices thereby directly obtaining information from individual cells. However, present solutions have no external communication capabilities impairing practical use. This project will design and engineer biological cells that can transmit information to neighboring cells and cells placed far away enabling nanoscale electronic devices thereby creating macro-structures or synthetic tissues. Our vision and overall goal is to enable "cells to wirelessly connect to the Internet". Towards this vision we have established a transdisciplinary team of researchers with international stature and expertise in synthetic and stem cell biology, communications engineering, and clinical medicine to develop cellular communication and control systems and test their performance. This project will design and develop a wireless sensor and actuator network of engineered cells that can sense and communication information for monitoring and deliver therapy. The developed engineered cells will be tested in cell and organoid cultures with imaging tools. The developed theories on information transfer between cells and control techniques for remote stimulation for therapy delivery will be simulated in a custom developed computer simulator and verified with the in-vitro experimental data. The project will recruit and train 1 PhD student and 2 Postdocs and has drawn up a comprehensive, multifaceted plan to disseminate, communicate and exploit the project results.