Abstract
Polar assembly (a feature of many natural protein-based fibrous structures, such as actin, microtubules, intermediate filaments, and collagens) is demonstrated in a straightforward, synthetic, peptide-based fiber system of de novo design (see false-color confocal-microscope image of fibers). This finding opens up possibilities for engineering self-assembling soft materials from the bottom up and with nano-to-microscale precision.
Self-assembling systems are found extensively in biology.1 An improved understanding of these systems would fuel efforts to engineer novel, bioinspired assemblies through de novo design. Interest in the area is intense because an ability to engineer or design water-soluble self-assembling systems offers routes to novel biomaterials with potential applications in nanobiotechnology.2–6
Self-assembling systems based on peptides, proteins, DNA, and RNA are all being explored.2–6 Furthermore, “living templates”, namely fungal hyphae, are being used to direct the hierarchical assembly of nanoparticles.7 Our focus has been on peptide-based assemblies.8–10 Specifically, we are interested in making self-assembling fibers and networks from straightforward, synthetically accessible peptide building blocks.
Considerable work has been done to mimic fibrous protein assemblies by using predominantly β-structured peptides that form amyloid-like fibrils.2, 11, 12 Relatively less has been done with α-helix-based assemblies.3, 8, 13 We have focused on fibrous assemblies based on the α-helical coiled coil, which is a widespread and well-understood protein–protein interaction motif.14–16
Specifically, we have combined rules for coiled-coil assembly to design a self-assembling-fiber (SAF) system comprising two complementary peptides, SAF-p1 and SAF-p2.8 Unlike natural and previously designed coiled coils, which form blunt-ended structures,14, 17 the SAF peptides were engineered to make offset dimers with complementary sticky ends to promote longitudinal assembly into fibers (Figure 1). Helical assembly was confirmed by using circular dichroism spectroscopy and X-ray fiber diffraction,8 and more recently by FTIR spectroscopy (unpublished data). Fiber formation was confirmed by electron microscopy (EM), which revealed that the fibers were linear, extended many microns, and were ≈45 nm thick:8 approximately 20 times thicker than expected for coiled-coil dimers.18 One explanation for thickening is that two-chain assemblies form nascent structures (protofibrils) that assemble further laterally to form the matured, thick fibers (Figure 1). Herein we describe experiments initially conceived to follow lateral assembly directly in water. We also show that this relatively straightforward system displays the unexpected and potentially exploitable feature of polar assembly.
Self-assembling systems are found extensively in biology.1 An improved understanding of these systems would fuel efforts to engineer novel, bioinspired assemblies through de novo design. Interest in the area is intense because an ability to engineer or design water-soluble self-assembling systems offers routes to novel biomaterials with potential applications in nanobiotechnology.2–6
Self-assembling systems based on peptides, proteins, DNA, and RNA are all being explored.2–6 Furthermore, “living templates”, namely fungal hyphae, are being used to direct the hierarchical assembly of nanoparticles.7 Our focus has been on peptide-based assemblies.8–10 Specifically, we are interested in making self-assembling fibers and networks from straightforward, synthetically accessible peptide building blocks.
Considerable work has been done to mimic fibrous protein assemblies by using predominantly β-structured peptides that form amyloid-like fibrils.2, 11, 12 Relatively less has been done with α-helix-based assemblies.3, 8, 13 We have focused on fibrous assemblies based on the α-helical coiled coil, which is a widespread and well-understood protein–protein interaction motif.14–16
Specifically, we have combined rules for coiled-coil assembly to design a self-assembling-fiber (SAF) system comprising two complementary peptides, SAF-p1 and SAF-p2.8 Unlike natural and previously designed coiled coils, which form blunt-ended structures,14, 17 the SAF peptides were engineered to make offset dimers with complementary sticky ends to promote longitudinal assembly into fibers (Figure 1). Helical assembly was confirmed by using circular dichroism spectroscopy and X-ray fiber diffraction,8 and more recently by FTIR spectroscopy (unpublished data). Fiber formation was confirmed by electron microscopy (EM), which revealed that the fibers were linear, extended many microns, and were ≈45 nm thick:8 approximately 20 times thicker than expected for coiled-coil dimers.18 One explanation for thickening is that two-chain assemblies form nascent structures (protofibrils) that assemble further laterally to form the matured, thick fibers (Figure 1). Herein we describe experiments initially conceived to follow lateral assembly directly in water. We also show that this relatively straightforward system displays the unexpected and potentially exploitable feature of polar assembly.
| Original language | English |
|---|---|
| Pages (from-to) | 325-328 |
| Number of pages | 4 |
| Journal | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION |
| Volume | 44 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Dec 2004 |