Characterizing the Impact of Communication on Cellular and Collective Behavior Using a Three-Dimensional Multiscale Cellular Model.

Communication between cells enables the coordination that drives structural and functional complexity in biological systems. Both single and multicellular organisms have evolved diverse communication systems for a range of purposes, including synchronization of behavior, division of labor, and spatial organization. Synthetic systems are also increasingly being engineered to utilize cell-cell communication. While research has elucidated the form and function of cell-cell communication in many biological systems, our knowledge is still limited by the confounding effects of other biological phenomena at play and the bias of the evolutionary background. In this work, our goal is to push forward the context-free understanding of what impact cell-cell communication can have on cellular and population behavior to more fully understand the extent to which cell-cell communication systems can be utilized, modified, and engineered. We use an in silico model of 3D multiscale cellular populations, with dynamic intracellular networks interacting via diffusible signals. We focus on two key communication parameters: the effective interaction distance at which cells are able to interact and the receptor activation threshold. We found that cell-cell communication can be divided into six different forms along the parameter axes, three asocial and three social. We also show that cellular behavior, tissue composition, and tissue diversity are all highly sensitive to both the general form and specific parameters of communication even when the cellular network has not been biased towards that behavior.

Flexibility of Boolean Network Reservoir Computers in Approximating Arbitrary Recursive and Non-Recursive Binary Filters.

Reservoir computers (RCs) are biology-inspired computational frameworks for signal processing that are typically implemented using recurrent neural networks. Recent work has shown that Boolean networks (BN) can also be used as reservoirs. We analyze the performance of BN RCs, measuring their flexibility and identifying the factors that determine the effective approximation of Boolean functions applied in a sliding-window fashion over a binary signal, both non-recursively and recursively. We train and test BN RCs of different sizes, signal connectivity, and in-degree to approximate three-bit, five-bit, and three-bit recursive binary functions, respectively. We analyze how BN RC parameters and function average sensitivity, which is a measure of function smoothness, affect approximation accuracy as well as the spread of accuracies for a single reservoir. We found that approximation accuracy and reservoir flexibility are highly dependent on RC parameters. Overall, our results indicate that not all reservoirs are equally flexible, and RC instantiation and training can be more efficient if this is taken into account. The optimum range of RC parameters opens up an angle of exploration for understanding how biological systems might be tuned to balance system restraints with processing capacity.

Computational capabilities of a multicellular reservoir computing system.

The capacity of cells to process information is currently used to design cell-based tools for ecological, industrial, and biomedical applications such as detecting dangerous chemicals or for bioremediation. In most applications, individual cells are used as the information processing unit. However, single cell engineering is limited by the necessary molecular complexity and the accompanying metabolic burden of synthetic circuits. To overcome these limitations, synthetic biologists have begun engineering multicellular systems that combine cells with designed subfunctions. To further advance information processing in synthetic multicellular systems, we introduce the application of reservoir computing. Reservoir computers (RCs) approximate a temporal signal processing task via a fixed-rule dynamic network (the reservoir) with a regression-based readout. Importantly, RCs eliminate the need of network rewiring, as different tasks can be approximated with the same reservoir. Previous work has already demonstrated the capacity of single cells, as well as populations of neurons, to act as reservoirs. In this work, we extend reservoir computing in multicellular populations with the widespread mechanism of diffusion-based cell-to-cell signaling. As a proof-of-concept, we simulated a reservoir made of a 3D community of cells communicating via diffusible molecules and used it to approximate a range of binary signal processing tasks, focusing on two benchmark functions-computing median and parity functions from binary input signals. We demonstrate that a diffusion-based multicellular reservoir is a feasible synthetic framework for performing complex temporal computing tasks that provides a computational advantage over single cell reservoirs. We also identified a number of biological properties that can affect the computational performance of these processing systems.