SynBioFromLeukipposInstitute

How researchers created complex tiling patterns with bioengineered bacteria

Adhesion molecules used to form multicellular patterns.

DeepMind says its AlphaFold tool has successfully predicted the structure of nearly all proteins known to science. The AI lab is offering its database of over 200 million proteins to anyone for free. 

To impart directionality to the motions of a molecular mechanism, one must overcome the random thermal forces that are ubiquitous on such small scales and in liquid solution at ambient temperature. In equilibrium without energy supply, directional motion cannot be sustained without violating the laws of thermodynamics. Under conditions away from thermodynamic equilibrium, directional motion may be achieved within the framework of Brownian ratchets, which are diffusive mechanisms that have broken inversion symmetry1–5. Ratcheting is thought to underpin the function of many natural biological motors, such as the F1F0-ATPase6–8, and it has been demonstrated experimentally in synthetic microscale systems (for example, to our knowledge, first in ref. 3) and also in artificial molecular motors created by organic chemical synthesis9–12. DNA nanotechnology13 has yielded a variety of nanoscale mechanisms, including pivots, hinges, crank sliders and rotary systems14–17, which can adopt different configurations, for example, triggered by strand-displacement reactions18,19 or by changing environmental parameters such as pH, ionic strength, temperature, external fields and by coupling their motions to those of natural motor proteins20–26. This previous work and considering low-Reynolds-number dynamics and inherent stochasticity27,28 led us to develop a nanoscale rotary motor built from DNA origami that is driven by ratcheting and whose mechanical capabilities approach those of biological motors such as F1F0-ATPase. A nanoscale rotary motor made of DNA origami, driven by ratcheting and powered by an external electric field, shows the ability to wind up a spring and has mechanical capabilities approaching those of biological motors.

The α-helix is pre-eminent in structural biology1 and widely exploited in protein folding2, design3 and engineering4. Although other helical peptide conformations do exist near to the α-helical region of conformational space—namely, 310-helices and π-helices5—these occur much less frequently in protein structures. Less favourable internal energies and reduced tendencies to pack into higher-order structures mean that 310-helices rarely exceed six residues in length in natural proteins, and that they tend not to form normal supersecondary, tertiary or quaternary interactions. Here we show that despite their absence in nature, synthetic peptide assemblies can be built from 310-helices. We report the rational design, solution-phase characterization and an X-ray crystal structure for water-soluble bundles of 310-helices with consolidated hydrophobic cores. The design uses six-residue repeats informed by analysing 310-helical conformations in known protein structures, and incorporates α-aminoisobutyric acid residues. Design iterations reveal a tipping point between α-helical and 310-helical folding, and identify features required for stabilizing assemblies of 310-helices. This work provides principles and rules to open opportunities for designing into this hitherto unexplored region of protein-structure space. A study demonstrates the rational de novo design of water-soluble assemblies constructed from long 310-helical peptides, and details their characterization by circular dichroism spectroscopy, analytical ultracentrifugation and X-ray crystallography.

A prototypical biocomposite block comprising a blend of bacteria, fungi and feedstock can be assembled into human-sized, living structures with self-healing and environmental sensing capabilities.

Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions1,2. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning3,4. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems5–8. However, our ability to engineer multicellular interface patterns2,9 is still very limited, as synthetic cell–cell adhesion toolkits and suitable patterning algorithms are underdeveloped5,7,10–13. Here we introduce a synthetic cell–cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials5–8,14. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems3,5. A synthetic cell-cell adhesion logic using swarming E. coli with 4 bits of information is introduced, enabling the programming of interfaces that combine to form universal tessellation patterns over a large scale.

A molecular rotary ratchet motor.

Cell biology; Stem cells research; Bioinformatics.