A self-assembly pathway to aligned monodomain gels

Journal name:
Nature Materials
Year published:
Published online


Aggregates of charged amphiphilic molecules have been found to access a structure at elevated temperature that templates alignment of supramolecular fibrils over macroscopic scales. The thermal pathway leads to a lamellar plaque structure with fibrous texture that breaks on cooling into large arrays of aligned nanoscale fibres and forms a strongly birefringent liquid. By manually dragging this liquid crystal from a pipette onto salty media, it is possible to extend this alignment over centimetres in noodle-shaped viscoelastic strings. Using this approach, the solution of supramolecular filaments can be mixed with cells at physiological temperatures to form monodomain gels of aligned cells and filaments. The nature of the self-assembly process and its biocompatibility would allow formation of cellular wires in situ that have any length and customized peptide compositions for use in biological applications.

At a glance


  1. Strings and gels with long-range internal alignment.
    Figure 1: Strings and gels with long-range internal alignment.

    a,b, A peptide amphiphile solution coloured with trypan blue injected into phosphate-buffered saline after heat treatment. c, The same solution dragged through a thin layer of aqueous CaCl2 to form a noodle-like string. d, A knot made with peptide amphiphile string. e, Birefringence of a bubble gel observed between cross polars suggesting the presence of macroscopically aligned domains. f, Similar domains in a gel film. g, Peptide amphiphile noodle spirals prepared on a spin coater. h, Birefringence of a single string suggesting alignment along the string axis. i, Light extinction between cross polars at the crosspoint of two noodles demonstrating uniform alignment in each.

  2. SEM evidence of massive alignment versus isotropy of nanofibre bundles.
    Figure 2: SEM evidence of massive alignment versus isotropy of nanofibre bundles.

    a,c, Aligned nanofibre bundles in macroscopic strings formed by dragging thermally treated amphiphile solutions onto a CaCl2 solution. b,d, Isotropic network of nanofibre bundles formed by adding CaCl2 to unheated amphiphile solutions. e,f, SAXS of hydrogel strings prepared using peptide amphiphile solutions with and without heat treatment.

  3. Morphological changes resulting from thermal treatment.
    Figure 3: Morphological changes resulting from thermal treatment.

    a, TEM obtained after a QFDE preparation of peptide amphiphile solution at 80 °C revealing a micrometre-sized, sheet-like plaque structure. b, Higher-resolution QFDE-TEM of the sheet-like structures revealing a surface pattern with a periodicity of about 7.5 nm. c, SAXS of peptide amphiphile solutions treated at different thermal conditions. d, QFDE-TEM of aligned nanofibre bundles templated by the sheet-like plaque after the peptide amphiphile solution was cooled to room temperature. e, SEM of plaques that were captured by adding CaCl2 at 80 °C. f, SEM of a plaque breaking into nanofibre bundles. g,h, Schematic representation of a plaque at high temperature (g) and its rupture into fused bundles on cooling (h). i,j, Schematic representation of the cross-section of a plaque formed by fused fibres (i) and of a fibre bundle (j).

  4. Cell alignment in strings of aligned filaments.
    Figure 4: Cell alignment in strings of aligned filaments.

    a, Preferential alignment of encapsulated hMSCs along the string axis. b, Calcein-labelled aligned cells cultured in string. c, SEM images at different magnifications of a single cell in a string (inset is the zoom-out view; the arrow indicates the alignment direction). d, A conductive black string formed by dispersing carbon nanotubes in peptide amphiphile solutions before heating. The SEM micrograph on the right shows aligned nanofibre bundles in the black string. e, Top: calcium fluorescence image of HL-1 cardiomyocytes encapsulated in a noodle-like string. Below: successive spatial maps of calcium fluorescence intensity travelling at 80-ms intervals, showing the propagation of an electrical signal throughout the entire string and demonstrating a functional cardiac syncytium. f, Calcium fluorescence intensity signal in time at three points in the string marked by colour in e, showing repeated propagating action potentials.


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Author information

  1. These authors contributed equally to this work

    • Shuming Zhang &
    • Megan A. Greenfield


  1. Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, USA

    • Shuming Zhang,
    • Jason R. Mantei,
    • Monica Olvera de la Cruz &
    • Samuel I. Stupp
  2. Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA

    • Megan A. Greenfield &
    • Monica Olvera de la Cruz
  3. Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, Illinois 60611, USA

    • Alvaro Mata,
    • Ronit Bitton,
    • Conrado Aparicio,
    • Monica Olvera de la Cruz &
    • Samuel I. Stupp
  4. Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA

    • Liam C. Palmer,
    • Monica Olvera de la Cruz &
    • Samuel I. Stupp
  5. Department of Medicine, Northwestern University, Chicago, Illinois 60611, USA

    • Samuel I. Stupp
  6. Present address: Nanotechnology Platform, Parc Cientific, 08028 Barcelona, Spain

    • Alvaro Mata


S.Z., M.A.G., A.M., L.C.P., R.B., C.A. and J.R.M. carried out experiments. M.A.G. and M.O.d.l.C. generated numerical data. M.A.G., M.O.d.l.C. and S.I.S developed a theoretical model. S.Z., M.A.G., L.C.P., R.B., J.R.M., M.O.d.l.C. and S.I.S. wrote the paper.

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