Biology subjects

Bogels, B.

Publications and source records attributed to Bogels, B..

3 recordsLinked to original sources

bioRxiv2023

Engineering a Scalable and Orthogonal Platform for Synthetic Communication in Mammalian Cells

The rational design and implementation of synthetic, orthogonal mammalian communication systems has the potential to unravel fundamental design principles of mammalian cell communication circuits and offer a framework for engineering of designer cell consortia with potential applications in cell therapeutics and artificial tissue engineering. We lay here the foundations for the engineering of an orthogonal, and scalable mammalian synthetic intercellular communication platform that exploits the programmability of synthetic receptors and selective affinity and tunability of diffusing coiled-coil (CC) peptide heterodimers. Leveraging the ability of CCs to exclusively bind to a selected cognate receptor, we demonstrate orthogonal receptor activation, as well as Boolean logic computations. Next, we reveal synthetic intercellular communication based on synthetic receptors and secreted multidomain CC ligands and demonstrate a minimal, three-cell population system that can perform distributed AND gate logic. Our work provides a modular and scalable framework for the engineering of complex cell consortia, with the potential to expand the aptitude of cell therapeutics and diagnostics.

synthetic biology↗

bioRxiv2020

Light-activated signaling in DNA-encoded sender-receiver architectures

Collective decision making by living cells is facilitated by exchange of diffusible signals where sender cells release a chemical signal that is interpreted by receiver cells. Biologists have started to unravel the underlying physicochemical determinants that control the effective communication distance using genetically modified cells. However, living systems are inherently challenging to manipulate and study systematically and quantitatively. Therefore, the development of generic and tunable abiotic mimics featuring compartmentalized signaling is highly desirable. Here, by adapting a previously reported artificial cell-cell communication system, we engineer DNA-encoded sender-receiver architectures, where protein-polymer microcapsules act as cell mimics and molecular communication occurs through diffusive DNA signals. We prepare spatial distributions of sender and receiver protocells using a microfluidic trapping array, and setup a signaling gradient from a single sender cell using light, which activates surrounding receivers through DNA strand displacement. Our systematic analysis reveals how the effective signal range of a single sender is determined by various factors including the density and permeability of receivers, extracellular signal degradation, signal consumption and catalytic regeneration. In addition, we construct a three-population configuration where two sender cells are embedded in a dense array of receivers that implement Boolean logic and investigate spatial integration of non-identical input cues. The results advance our understanding of diffusion-based sender-receiver topologies and present a strategy for constructing spatially controlled chemical communication systems that have the potential to reconstitute collective cellular behavior.Competing Interest StatementThe authors have declared no competing interest.View Full Text

synthetic biology↗

bioRxiv2019

Distributed DNA-based Communication in Populations of Synthetic Protocells

Developing distributed communication platforms based on orthogonal molecular communication channels is a crucial step towards engineering artificial multicellular systems. Here, we present a general and scalable platform entitled Biomolecular Implementation of Protocellular Communication (BIO-PC) to engineer distributed multichannel molecular communication between populations of non-lipid semipermeable microcapsules. Our method leverages the modularity and scalability of enzyme-free DNA strand-displacement circuits to develop protocellular consortia that can sense, process and respond to DNA-based messages. We engineer a rich variety of biochemical communication devices capable of cascaded amplification, bidirectional communication and distributed computational operations. Encapsulating DNA strand-displacement circuits further allows their use in concentrated serum where non-compartmentalized DNA circuits cannot operate. BIO-PC enables reliable execution of distributed DNA-based molecular programs in biologically relevant environments and opens new directions in DNA computing and minimal cell technology.

synthetic biology↗