Lateral heterogeneity and spatial patterning of proteins observed in biological membranes have been accredited to a wide variety of phenomena including lipid rafts, phase separation and curvature recognition, but remain poorly understood.Here, we found that a biological reaction-diffusion system, the Escherichia coli MinDE system, induces patterns and gradients of completely unrelated membrane-bound macromolecules by a non-specific mechanism. A paradigm for pattern formation, the MinDE system is based on the ATPase MinD, its activator MinE and the membrane as a reaction matrix. This minimal oscillator defines midcell in E. coli. Using a well-established in vitro reconstitution assay on supported lipid bilayers we show that MinDE dynamics are able to spatiotemporally regulate functionally unrelated membrane proteins. Intriguingly, the ATP-driven MinDE self-organization induced directed and active net transport of lipid-anchored proteins, establishing large-scale gradients on the membrane. To interrogate the phenomenon in a defined manner we employed this simplistic transport mechanism for positioning of a synthetic cargo: membrane-anchored DNA nanostructures. By varying the number of membrane anchors and the size of the highly controllable DNA origami we determined the influence of cargo properties on its spatiotemporal positioning by MinDE. We find that the diffusion coefficient and the membrane footprint of the target molecule determine the extent of the regulation. Using this knowledge, we are able to sort and spatially separate DNA origami according to the number of membrane anchors by MinDE self-organization. These findings imply that MinDE are able to position a much larger set of proteins in the cell than previously known. We further speculate that also other reaction-diffusion systems are capable of regulating a large set of proteins by similar non-specific interactions, hinting towards a generic mechanism to couple ATP consumption to protein patterning and sorting.

Elsevier/ Cell Press
Biophys. J.
Physics of Cellular Interactions

Ramm, B., Khmelinskaia, A., Blumhardt, P., Eto, H., Ganzinger, K., & Schwille, P. (2020). Molecular Transport and Spatial Sorting of Membrane-bound DNA Nanostructures by a Biological Reaction-diffusion System. In Biophys. J. (Vol. 118, pp. 165A–165A). doi:10.1016/j.bpj.2019.11.1017