---
OA_place: repository
OA_type: green
_id: '21749'
abstract:
- lang: eng
  text: The collagen triple helix assembles hierarchically into bundled oligomers,
    solvated networks, and fibers. Synthetic peptide assemblies, driven by supramolecular
    interactions, can form single triple helices through intrahelical amino acid pairs;
    however, the principles guiding interhelical associations into higher-order structures
    remain unclear. Here, we incorporate cation−π and electrostatic charge pairs to
    probe interhelical interactions and elucidate the mechanisms driving triple helix
    assembly into fibrils, nanotubes, and nanosheets. Introducing cation−π pairs into
    a fibrillating collagen mimetic resulted in D-periodic fibrils with pH-sensitive
    gelation. By alternating the presentation of electrostatic and cation−π pairs,
    the assembly of another D-periodic fibril featuring inner and outer triple-helical
    layers was resolved by cryo electron microscopy to a resolution of 8 Å. At physiological
    pH, antiparallel association of these triple helices leads to the formation of
    nanotubes. The packing behavior of triple helices correlates with the interhelical
    interactions, where parallel associations favor fibril formation and antiparallel
    interactions drive nanotube and nanosheet assembly. These self-assembling triple-helical
    peptides demonstrate how packing of higher-order structures can be tailored with
    supramolecular interactions and establish the relationship of different hierarchical
    collagen-mimetic assemblies as pH-dependent.
acknowledgement: The authors acknowledge Crispin Hetherington and L. Tracy Yu for
  their technical assistance and insights. This work was funded in part by the National
  Science Foundation (CHE 2203937), the National Science Foundation Graduate Research
  Fellowship (Grant No. 1842494), the Welch Foundation (C-2141), the Swedish Research
  Council (2020-04633), and the NIH (GM122510). This work benefited from using the
  SasView application, originally developed under NSF award DMR-0520547. SasView contains
  code developed with funding from the European Union’s Horizon 2020 research and
  innovation program under the SINE2020 project, Grant Agreement No. 654000. This
  work was partly done using the Shared Equipment Authority resources at Rice University.
article_processing_charge: No
article_type: original
author:
- first_name: Carson C.
  full_name: Cole, Carson C.
  last_name: Cole
- first_name: Mark A.B.
  full_name: Kreutzberger, Mark A.B.
  last_name: Kreutzberger
- first_name: Kevin
  full_name: Klein, Kevin
  id: 1e7ede04-9e54-11f0-9ec4-8d4d5563c398
  last_name: Klein
- first_name: Kiana A.
  full_name: Cahue, Kiana A.
  last_name: Cahue
- first_name: Brett H.
  full_name: Pogostin, Brett H.
  last_name: Pogostin
- first_name: Adam C.
  full_name: Farsheed, Adam C.
  last_name: Farsheed
- first_name: Joseph W.R.
  full_name: Swain, Joseph W.R.
  last_name: Swain
- first_name: Thi H.
  full_name: Bui, Thi H.
  last_name: Bui
- first_name: Arghadip
  full_name: Dey, Arghadip
  last_name: Dey
- first_name: Jonathan T.
  full_name: Makhoul, Jonathan T.
  last_name: Makhoul
- first_name: Marija
  full_name: Dubackic, Marija
  last_name: Dubackic
- first_name: Antara
  full_name: Pal, Antara
  last_name: Pal
- first_name: Ulf
  full_name: Olsson, Ulf
  last_name: Olsson
- first_name: Anđela
  full_name: Šarić, Anđela
  id: bf63d406-f056-11eb-b41d-f263a6566d8b
  last_name: Šarić
  orcid: 0000-0002-7854-2139
- first_name: Edward H.
  full_name: Egelman, Edward H.
  last_name: Egelman
- first_name: Jeffrey D.
  full_name: Hartgerink, Jeffrey D.
  last_name: Hartgerink
citation:
  ama: Cole CC, Kreutzberger MAB, Klein K, et al. Supramolecular assembly of collagen-mimetic
    eptide D-periodic fibrils and nanoassemblies. <i>Biomacromolecules</i>. 2026;27(4):2956-2965.
    doi:<a href="https://doi.org/10.1021/acs.biomac.6c00345">10.1021/acs.biomac.6c00345</a>
  apa: Cole, C. C., Kreutzberger, M. A. B., Klein, K., Cahue, K. A., Pogostin, B.
    H., Farsheed, A. C., … Hartgerink, J. D. (2026). Supramolecular assembly of collagen-mimetic
    eptide D-periodic fibrils and nanoassemblies. <i>Biomacromolecules</i>. American
    Chemical Society. <a href="https://doi.org/10.1021/acs.biomac.6c00345">https://doi.org/10.1021/acs.biomac.6c00345</a>
  chicago: Cole, Carson C., Mark A.B. Kreutzberger, Kevin Klein, Kiana A. Cahue, Brett
    H. Pogostin, Adam C. Farsheed, Joseph W.R. Swain, et al. “Supramolecular Assembly
    of Collagen-Mimetic Eptide D-Periodic Fibrils and Nanoassemblies.” <i>Biomacromolecules</i>.
    American Chemical Society, 2026. <a href="https://doi.org/10.1021/acs.biomac.6c00345">https://doi.org/10.1021/acs.biomac.6c00345</a>.
  ieee: C. C. Cole <i>et al.</i>, “Supramolecular assembly of collagen-mimetic eptide
    D-periodic fibrils and nanoassemblies,” <i>Biomacromolecules</i>, vol. 27, no.
    4. American Chemical Society, pp. 2956–2965, 2026.
  ista: Cole CC, Kreutzberger MAB, Klein K, Cahue KA, Pogostin BH, Farsheed AC, Swain
    JWR, Bui TH, Dey A, Makhoul JT, Dubackic M, Pal A, Olsson U, Šarić A, Egelman
    EH, Hartgerink JD. 2026. Supramolecular assembly of collagen-mimetic eptide D-periodic
    fibrils and nanoassemblies. Biomacromolecules. 27(4), 2956–2965.
  mla: Cole, Carson C., et al. “Supramolecular Assembly of Collagen-Mimetic Eptide
    D-Periodic Fibrils and Nanoassemblies.” <i>Biomacromolecules</i>, vol. 27, no.
    4, American Chemical Society, 2026, pp. 2956–65, doi:<a href="https://doi.org/10.1021/acs.biomac.6c00345">10.1021/acs.biomac.6c00345</a>.
  short: C.C. Cole, M.A.B. Kreutzberger, K. Klein, K.A. Cahue, B.H. Pogostin, A.C.
    Farsheed, J.W.R. Swain, T.H. Bui, A. Dey, J.T. Makhoul, M. Dubackic, A. Pal, U.
    Olsson, A. Šarić, E.H. Egelman, J.D. Hartgerink, Biomacromolecules 27 (2026) 2956–2965.
date_created: 2026-04-19T22:07:46Z
date_published: 2026-04-13T00:00:00Z
date_updated: 2026-05-06T05:43:44Z
day: '13'
department:
- _id: AnSa
doi: 10.1021/acs.biomac.6c00345
intvolume: '        27'
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2025.02.15.637692
month: '04'
oa: 1
oa_version: Preprint
page: 2956-2965
publication: Biomacromolecules
publication_identifier:
  eissn:
  - 1526-4602
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Supramolecular assembly of collagen-mimetic eptide D-periodic fibrils and nanoassemblies
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 27
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
_id: '17239'
abstract:
- lang: eng
  text: Collagen is the most abundant protein in tissue scaffolds in live organisms.
    Collagen can self-assemble in vitro, which has led to a number of biotechnological
    and biomedical applications. To understand the dominant factors that participate
    in the formation of collagen nanostructures, here we study in real time and with
    nanoscale resolution the disassembly and reassembly of collagens. We implement
    a high-speed force microscope, which provides in situ high spatiotemporal resolution
    images of collagen nanostructures under changing pH conditions. The disassembly
    and reassembly are dominated by the electrostatic interactions among amino-acid
    residues of different molecules. Acidic conditions favor disassembly by neutralizing
    negatively charged residues. The process sets a net repulsive force between collagen
    molecules. A neutral pH favors the presence of negative and positively charged
    residues along the collagen molecules, which promotes their electrostatic attraction.
    Molecular dynamics simulations reproduce the experimental behavior and validate
    the electrostatic-based model of the disassembly and reassembly processes.
acknowledgement: We are grateful to Nancy Forde (Simon Fraser University) for her
  motivating comments. Financial support from the Ministerio de Ciencia, Innovación
  y Universidades (PID2019-106801GB-I00 and PID2022-136851NB-I00) is acknowledged.
  A.Š. and K.K. acknowledge support from the Royal Society University Research Fellowship
  and ERC the European Union’s Horizon 2020584 Research and Innovation Programme (Grant
  No. 585 80296).
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Clara
  full_name: Garcia-Sacristan, Clara
  last_name: Garcia-Sacristan
- first_name: Victor G.
  full_name: Gisbert, Victor G.
  last_name: Gisbert
- first_name: Kevin
  full_name: Klein, Kevin
  id: 1e7ede04-9e54-11f0-9ec4-8d4d5563c398
  last_name: Klein
- first_name: Anđela
  full_name: Šarić, Anđela
  id: bf63d406-f056-11eb-b41d-f263a6566d8b
  last_name: Šarić
  orcid: 0000-0002-7854-2139
- first_name: Ricardo
  full_name: Garcia, Ricardo
  last_name: Garcia
citation:
  ama: Garcia-Sacristan C, Gisbert VG, Klein K, Šarić A, Garcia R. In operando imaging
    electrostatic-driven disassembly and reassembly of collagen nanostructures. <i>ACS
    Nano</i>. 2024;18(28):18485-18492. doi:<a href="https://doi.org/10.1021/acsnano.4c03839">10.1021/acsnano.4c03839</a>
  apa: Garcia-Sacristan, C., Gisbert, V. G., Klein, K., Šarić, A., &#38; Garcia, R.
    (2024). In operando imaging electrostatic-driven disassembly and reassembly of
    collagen nanostructures. <i>ACS Nano</i>. American Chemical Society. <a href="https://doi.org/10.1021/acsnano.4c03839">https://doi.org/10.1021/acsnano.4c03839</a>
  chicago: Garcia-Sacristan, Clara, Victor G. Gisbert, Kevin Klein, Anđela Šarić,
    and Ricardo Garcia. “In Operando Imaging Electrostatic-Driven Disassembly and
    Reassembly of Collagen Nanostructures.” <i>ACS Nano</i>. American Chemical Society,
    2024. <a href="https://doi.org/10.1021/acsnano.4c03839">https://doi.org/10.1021/acsnano.4c03839</a>.
  ieee: C. Garcia-Sacristan, V. G. Gisbert, K. Klein, A. Šarić, and R. Garcia, “In
    operando imaging electrostatic-driven disassembly and reassembly of collagen nanostructures,”
    <i>ACS Nano</i>, vol. 18, no. 28. American Chemical Society, pp. 18485–18492,
    2024.
  ista: Garcia-Sacristan C, Gisbert VG, Klein K, Šarić A, Garcia R. 2024. In operando
    imaging electrostatic-driven disassembly and reassembly of collagen nanostructures.
    ACS Nano. 18(28), 18485–18492.
  mla: Garcia-Sacristan, Clara, et al. “In Operando Imaging Electrostatic-Driven Disassembly
    and Reassembly of Collagen Nanostructures.” <i>ACS Nano</i>, vol. 18, no. 28,
    American Chemical Society, 2024, pp. 18485–92, doi:<a href="https://doi.org/10.1021/acsnano.4c03839">10.1021/acsnano.4c03839</a>.
  short: C. Garcia-Sacristan, V.G. Gisbert, K. Klein, A. Šarić, R. Garcia, ACS Nano
    18 (2024) 18485–18492.
date_created: 2024-07-14T22:01:12Z
date_published: 2024-07-16T00:00:00Z
date_updated: 2025-12-16T09:01:10Z
day: '16'
ddc:
- '540'
department:
- _id: AnSa
doi: 10.1021/acsnano.4c03839
ec_funded: 1
external_id:
  isi:
  - '001263155500001'
  pmid:
  - '38958189'
file:
- access_level: open_access
  checksum: b7e9ce718e92f568bcb3810e8e28e458
  content_type: application/pdf
  creator: dernst
  date_created: 2025-01-09T12:06:48Z
  date_updated: 2025-01-09T12:06:48Z
  file_id: '18808'
  file_name: 2024_ACSNano_GarciaSacristan.pdf
  file_size: 10036838
  relation: main_file
  success: 1
file_date_updated: 2025-01-09T12:06:48Z
has_accepted_license: '1'
intvolume: '        18'
isi: 1
issue: '28'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 18485-18492
pmid: 1
project:
- _id: eba2549b-77a9-11ec-83b8-a81e493eae4e
  call_identifier: H2020
  grant_number: '802960'
  name: 'Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines'
publication: ACS Nano
publication_identifier:
  eissn:
  - 1936-086X
  issn:
  - 1936-0851
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: In operando imaging electrostatic-driven disassembly and reassembly of collagen
  nanostructures
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 18
year: '2024'
...