Genetically encoded lipid–polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly


Post-translational modification of proteins is a strategy widely used in biological systems. It expands the diversity of the proteome and allows for tailoring of both the function and localization of proteins within cells as well as the material properties of structural proteins and matrices. Despite their ubiquity in biology, with a few exceptions, the potential of post-translational modifications in biomaterials synthesis has remained largely untapped. As a proof of concept to demonstrate the feasibility of creating a genetically encoded biohybrid material through post-translational modification, we report here the generation of a family of three stimulus-responsive hybrid materials—fatty-acid-modified elastin-like polypeptides—using a one-pot recombinant expression and post-translational lipidation methodology. These hybrid biomaterials contain an amphiphilic domain, composed of a β-sheet-forming peptide that is post-translationally functionalized with a C14 alkyl chain, fused to a thermally responsive elastin-like polypeptide. They exhibit temperature-triggered hierarchical self-assembly across multiple length scales with varied structure and material properties that can be controlled at the sequence level.

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Fig. 1: Schematic of the structure and synthesis of FAMEs through post-translational modification of ELPs.
Fig. 2: Temperature-triggered macroscale self-assembly of FAMEs.
Fig. 3: DLS and spectroscopic  characterization of the effect of myristoylation on the structure and self-assembly of FAMEs.
Fig. 4: Characterization of the morphology of the FAME aggregates and visualization of their temperature-triggered phase transition and self-assembly across different length scales and temperatures.
Fig. 5: SEM morphological characterization of the macroscopic aggregates formed by heating M–B2–ELP and M–B3–ELP.
Fig. 6: Proposed three-step mechanism of FAME self-assembly.


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This research was funded by the National Science Foundation (NSF) through the Research Triangle Materials Research Science and Engineering Center (MRSEC; DMR-1121107) and by the National Institutes of Health (NIH; R01 GM-061232). Duke University Shared Materials Instrumentation Facility (SMIF) and Analytical Instrumentation facility (AIF) at North Carolina State University are members of the North Carolina Research Triangle NanotechnologyNetwork (RTNN), which is supported by the NSF (ECCS-1542015) as part of the National Nanotechnology Coordinated Infrastructure (NNCI). The authors thank K. Franz for access to chromatography instrumentation and the peptide synthesizer, J.G. Mark for conducting SDCLM experiments and M. Plue for the SEM imaging. The authors also thank H. Burg for her support in SFM sample preparation and analysis, M.-J. van Zadel for assistance with the variable-temperature ATR-IR experiments and M. Rubinstein for suggestions regarding the mechanism of self-assembly.

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D.M., K.M.L. and A.C. designed and performed experiments, analysed data and wrote the manuscript. J.R.S., M.D., R.B., H.S.V., S.H.P., F.C.H., K.L.B., N.R.M., I.W. and M.B. performed experiments, analysed data and took part in discussions.

Correspondence to Ashutosh Chilkoti.

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Supplementary methods, data, analysis; Supplementary figures 1–4; Supplementary tables 1–6

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Mozhdehi, D., Luginbuhl, K.M., Simon, J.R. et al. Genetically encoded lipid–polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly. Nature Chem 10, 496–505 (2018).

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