Abstract
Synthetic biology provides an opportunity for the construction and exploration of alternative solutions to biological problems - solutions different from those chosen by natural life. To this end, synthetic biologists have built new sensory systems, cellular memories, and alternative genetic codes. There is a growing interest in applying synthetic approaches to multicellular systems, especially in relation to multicellular self-organization. Here we describe a synthetic biological system that confers large-scale de novo patterning activity on 2-D and 3-D populations of mammalian cells. Instead of using the reaction-diffusion mechanisms common in real embryos, our system uses cadherin-mediated phase separation, inspired by the known phenomenon of cadherin-based sorting. An engineered self-organizing, large-scale patterning system requiring no prior spatial cue may be a significant step towards the construction of self-assembling synthetic tissues.
Highlights
Animal systems, cell movement may interfere with the establishment of pattern when movement is fast compared to the response times in the feedback systems
Cadherins are a family of over 100 calcium-dependent cell adhesion molecules, the ‘classical’ members of which can bind both homotypically or heterotypically[26]
We added a similar Cdh[3] (P-cadherin) module, pTREx-mCherry2A-Cdh[3] to the library (Fig. 1a) because the differential adhesive strengths between homotypic and heterotypic E-cadherin and P-cadherin interactions have been reported to drive cell sorting when these cadherins are expressed in mammalian cells[27]
Summary
Animal systems, cell movement may interfere with the establishment of pattern when movement is fast compared to the response times in the feedback systems. For example, can be in high- or low-motility phases: high population densities cause individuals to exhibit low motility, so that exploring individuals become ‘trapped’ where many of their kind already are, depleting intervening spaces[18] This generates alternative patterns of mussel beds and spaces. Compared with reaction-diffusion systems, phase separation systems have the advantage that pattern generating action is less dependent on parameters being in the correct range ( the parameters do still control the nature of the pattern formed and the speed with which it forms). They have the feature that they depend on cell movement, rather than being destabilized by it. Phase-separation may be of greatest use in animal-cell systems, whereas reaction diffusion may be more appropriate to plants
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