Abstract
Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels1,2, both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks3–13. However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs)14 can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains15,16 for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.
Original language | English |
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Pages (from-to) | 216-220 |
Number of pages | 5 |
Journal | Nature |
Volume | 577 |
Issue number | 7789 |
DOIs | |
State | Published - Jan 9 2020 |
Funding
Acknowledgements This work was supported by the US Department of Defense, Army Research Office, under contract W911NF-13-1-0232 and the National Science Foundation under contract DMR-183696. M.O.d.l.C. and B.Q. acknowledge support through grant DE-FG02-08ER46539 from the Department of Energy (DOE) Basic Energy Science Office and the Center for Computation and Theory of Soft Materials, as well as computational support by the Sherman Fairchild Foundation. Z. H. and M. R. acknowledge support from the Air Force Office of Sponsored Research Award FA9550-15-1-0273. A part of this research used resources at the High Flux Isotope Laboratory, a DOE Office of Science User Facility operated by the Oak Ridge National Laboratory. We acknowledge the support of the National Institute of Standards and Technology, US Department of Commerce, in providing the neutron research facilities used in this work. We thank L. He and Y. Liu for help in the SANS studies. Scattering studies at the Advanced Light Source and RHP characterization at the Molecular Foundry were supported by the Office of Science, Office of Basic Energy Sciences of the US DOE under contract DE-AC02-05CH11231. We thank A. A. A. Smith for help in polymer syntheses; Y. W. Qian for characterizing the liposome sizes; A. Martin and E. M. López-Alfonzo for help in stopped-flow experiments. We thank CoC-NMR for help with RHP characterization; instruments at CoC-NMR are supported in part by NIH S10OD024998.