A library of mammalian effector modules for synthetic morphology

Abstract

BackgroundIn mammalian development, the formation of most tissues is achieved by a relatively small repertoire of basic morphogenetic events (e.g. cell adhesion, locomotion, apoptosis, etc.), permutated in various sequences to form different tissues. Together with cell differentiation, these mechanisms allow populations of cells to organize themselves into defined geometries and structures, as simple embryos develop into complex organisms. The control of tissue morphogenesis by populations of engineered cells is a potentially very powerful but neglected aspect of synthetic biology.ResultsWe have assembled a modular library of synthetic morphogenetic driver genes to control (separately) mammalian cell adhesion, locomotion, fusion, proliferation and elective cell death. Here we describe this library and demonstrate its use in the T-REx-293 human cell line to induce each of these desired morphological behaviours on command.ConclusionsBuilding on from the simple test systems described here, we want to extend engineered control of morphogenetic cell behaviour to more complex 3D structures that can inform embryologists and may, in the future, be used in surgery and regenerative medicine, making synthetic morphology a powerful tool for developmental biology and tissue engineering.Electronic supplementary materialThe online version of this article (doi:10.1186/1754-1611-8-26) contains supplementary material, which is available to authorized users.

Synthetic biology meets tissue engineering

“…This observation has allowed us to produce a set of modules for ‘synthetic morphology’, that allow control of proliferation, elective cell death, cell fusion, cell adhesion and locomotion [5]. These have been published separately from work on patterning but, in principle, morphogenetic modules can be placed downstream of patterning.…”

“…Much engineering work, for example constructing modules for new metabolism or biosensing, has been done in single-celled microorganisms with little or no possibility for multicellular organization (examples may be found in [1–3]) and, even where host cells from multicellular organisms such as animals and plants have been used, multicellularity has usually been irrelevant to the aims of the project. A few projects have, however, focused on the behaviour of cell collectives, for example to synchronize synthetic oscillators [4] or to orchestrate simple multicellular morphogenetic events [5]. These projects have demonstrated the feasibility of constructing mechanisms that use cooperative actions of engineered cells and, we argue in this article, open the door to the application of synthetic biological techniques to the challenges of advanced tissue engineering.…”

Using synthetic biology to explore principles of development

“…7B) (Cachat et al, 2014 point of the library is to allow the behaviours to be triggered in specific orders and placed under the command of synthetic biological genetic systems . It may be possible, for example, for a morphogenetic module to be linked to a synthetic patterning system such as those described above, to 'reproduce' the natural sequence of 'patterning then morphogenesis'.…”

Synthetic Biology: Rational Pathway Design for Regenerative Medicine

“…We have now built some of these modules and have shown that they function as intended, at least at the level of cell behaviour in culture [25]. Specifically, they confer on human cells controllable proliferation, apoptosis, adhesion, locomotion and formation of syncytia.…”