---
_id: '11841'
abstract:
- lang: eng
text: Primary nucleation is the fundamental event that initiates the conversion
of proteins from their normal physiological forms into pathological amyloid aggregates
associated with the onset and development of disorders including systemic amyloidosis,
as well as the neurodegenerative conditions Alzheimer’s and Parkinson’s diseases.
It has become apparent that the presence of surfaces can dramatically modulate
nucleation. However, the underlying physicochemical parameters governing this
process have been challenging to elucidate, with interfaces in some cases having
been found to accelerate aggregation, while in others they can inhibit the kinetics
of this process. Here we show through kinetic analysis that for three different
fibril-forming proteins, interfaces affect the aggregation reaction mainly through
modulating the primary nucleation step. Moreover, we show through direct measurements
of the Gibbs free energy of adsorption, combined with theory and coarse-grained
computer simulations, that overall nucleation rates are suppressed at high and
at low surface interaction strengths but significantly enhanced at intermediate
strengths, and we verify these regimes experimentally. Taken together, these results
provide a quantitative description of the fundamental process which triggers amyloid
formation and shed light on the key factors that control this process.
acknowledgement: "The research leading to these results has received funding from
the European Research Council (ERC) under the European Union’s Seventh Framework
Programme (FP7/2007-2013) through the ERC grant PhysProt\r\n(agreement 337969).
We are grateful for financial support from the Biotechnology and Biological Sciences
Research Council (BBSRC) (T.P.J.K.), the Newman\r\nFoundation (T.P.J.K.), the Wellcome
Trust (T.P.J.K. and M.V.), Peterhouse College\r\nCambridge (T.C.T.M.), the ERC Starting
Grant (StG) Non-Equilibrium Protein Assembly (NEPA) (A.S.), the Royal Society (A.S.),
the Academy of Medical Sciences\r\n(A.S. and J.K.), and the Cambridge Centre for
Misfolding Diseases (CMD)."
article_number: e2109718119
article_processing_charge: No
article_type: original
author:
- first_name: Zenon
full_name: Toprakcioglu, Zenon
last_name: Toprakcioglu
- first_name: Ayaka
full_name: Kamada, Ayaka
last_name: Kamada
- first_name: Thomas C.T.
full_name: Michaels, Thomas C.T.
last_name: Michaels
- first_name: Mengqi
full_name: Xie, Mengqi
last_name: Xie
- first_name: Johannes
full_name: Krausser, Johannes
last_name: Krausser
- first_name: Jiapeng
full_name: Wei, Jiapeng
last_name: Wei
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: Michele
full_name: Vendruscolo, Michele
last_name: Vendruscolo
- first_name: Tuomas P.J.
full_name: Knowles, Tuomas P.J.
last_name: Knowles
citation:
ama: Toprakcioglu Z, Kamada A, Michaels TCT, et al. Adsorption free energy predicts
amyloid protein nucleation rates. Proceedings of the National Academy of Sciences
of the United States of America. 2022;119(31). doi:10.1073/pnas.2109718119
apa: Toprakcioglu, Z., Kamada, A., Michaels, T. C. T., Xie, M., Krausser, J., Wei,
J., … Knowles, T. P. J. (2022). Adsorption free energy predicts amyloid protein
nucleation rates. Proceedings of the National Academy of Sciences of the United
States of America. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2109718119
chicago: Toprakcioglu, Zenon, Ayaka Kamada, Thomas C.T. Michaels, Mengqi Xie, Johannes
Krausser, Jiapeng Wei, Anđela Šarić, Michele Vendruscolo, and Tuomas P.J. Knowles.
“Adsorption Free Energy Predicts Amyloid Protein Nucleation Rates.” Proceedings
of the National Academy of Sciences of the United States of America. Proceedings
of the National Academy of Sciences, 2022. https://doi.org/10.1073/pnas.2109718119.
ieee: Z. Toprakcioglu et al., “Adsorption free energy predicts amyloid protein
nucleation rates,” Proceedings of the National Academy of Sciences of the United
States of America, vol. 119, no. 31. Proceedings of the National Academy of
Sciences, 2022.
ista: Toprakcioglu Z, Kamada A, Michaels TCT, Xie M, Krausser J, Wei J, Šarić A,
Vendruscolo M, Knowles TPJ. 2022. Adsorption free energy predicts amyloid protein
nucleation rates. Proceedings of the National Academy of Sciences of the United
States of America. 119(31), e2109718119.
mla: Toprakcioglu, Zenon, et al. “Adsorption Free Energy Predicts Amyloid Protein
Nucleation Rates.” Proceedings of the National Academy of Sciences of the United
States of America, vol. 119, no. 31, e2109718119, Proceedings of the National
Academy of Sciences, 2022, doi:10.1073/pnas.2109718119.
short: Z. Toprakcioglu, A. Kamada, T.C.T. Michaels, M. Xie, J. Krausser, J. Wei,
A. Šarić, M. Vendruscolo, T.P.J. Knowles, Proceedings of the National Academy
of Sciences of the United States of America 119 (2022).
date_created: 2022-08-14T22:01:45Z
date_published: 2022-07-28T00:00:00Z
date_updated: 2023-10-04T09:06:52Z
day: '28'
ddc:
- '570'
department:
- _id: AnSa
doi: 10.1073/pnas.2109718119
ec_funded: 1
external_id:
isi:
- '000903753500002'
file:
- access_level: open_access
checksum: 0fe3878896cbeb6c44e29222ec2f336a
content_type: application/pdf
creator: dernst
date_created: 2023-10-04T09:05:44Z
date_updated: 2023-10-04T09:05:44Z
file_id: '14386'
file_name: 2022_PNAS_Toprakcioglu.pdf
file_size: 2476021
relation: main_file
success: 1
file_date_updated: 2023-10-04T09:05:44Z
has_accepted_license: '1'
intvolume: ' 119'
isi: 1
issue: '31'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '07'
oa: 1
oa_version: Published Version
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: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: Proceedings of the National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Adsorption free energy predicts amyloid protein nucleation rates
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 119
year: '2022'
...
---
_id: '12108'
abstract:
- lang: eng
text: The sequential exchange of filament composition to increase filament curvature
was proposed as a mechanism for how some biological polymers deform and cut membranes.
The relationship between the filament composition and its mechanical effect is
lacking. We develop a kinetic model for the assembly of composite filaments that
includes protein–membrane adhesion, filament mechanics and membrane mechanics.
We identify the physical conditions for such a membrane remodeling and show this
mechanism of sequential polymer assembly lowers the energetic barrier for membrane
deformation.
acknowledgement: "We thank T. C. T. Michaels and J. Palacci for useful discussions.
We thank Claudia Flandoli for the illustrations in Fig. 1(b) and Fig. 2. We acknowledge
funding by the European Union’s Horizon 2020 Research and Innovation Programme under
the Marie Skłodowska-Curie Grant\r\nAgreement No. 101034413 (I. P.), the Royal Society
Grant No. UF160266 (A. Š.), the European Research Council under the European Union’s
Horizon 2020 Research and Innovation Programme (Grant No. 802960; B. M., I. P.,
and A. Š.), and the Volkswagen Foundation\r\nLife Grant (B. B. and A. Š). "
article_number: '268101'
article_processing_charge: No
article_type: original
author:
- first_name: Billie
full_name: Meadowcroft, Billie
id: a4725fd6-932b-11ed-81e2-c098c7f37ae1
last_name: Meadowcroft
- first_name: Ivan
full_name: Palaia, Ivan
id: 9c805cd2-4b75-11ec-a374-db6dd0ed57fa
last_name: Palaia
orcid: ' 0000-0002-8843-9485 '
- first_name: Anna Katharina
full_name: Pfitzner, Anna Katharina
last_name: Pfitzner
- first_name: Aurélien
full_name: Roux, Aurélien
last_name: Roux
- first_name: Buzz
full_name: Baum, Buzz
last_name: Baum
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
citation:
ama: Meadowcroft B, Palaia I, Pfitzner AK, Roux A, Baum B, Šarić A. Mechanochemical
rules for shape-shifting filaments that remodel membranes. Physical Review
Letters. 2022;129(26). doi:10.1103/PhysRevLett.129.268101
apa: Meadowcroft, B., Palaia, I., Pfitzner, A. K., Roux, A., Baum, B., & Šarić,
A. (2022). Mechanochemical rules for shape-shifting filaments that remodel membranes.
Physical Review Letters. American Physical Society. https://doi.org/10.1103/PhysRevLett.129.268101
chicago: Meadowcroft, Billie, Ivan Palaia, Anna Katharina Pfitzner, Aurélien Roux,
Buzz Baum, and Anđela Šarić. “Mechanochemical Rules for Shape-Shifting Filaments
That Remodel Membranes.” Physical Review Letters. American Physical Society,
2022. https://doi.org/10.1103/PhysRevLett.129.268101.
ieee: B. Meadowcroft, I. Palaia, A. K. Pfitzner, A. Roux, B. Baum, and A. Šarić,
“Mechanochemical rules for shape-shifting filaments that remodel membranes,” Physical
Review Letters, vol. 129, no. 26. American Physical Society, 2022.
ista: Meadowcroft B, Palaia I, Pfitzner AK, Roux A, Baum B, Šarić A. 2022. Mechanochemical
rules for shape-shifting filaments that remodel membranes. Physical Review Letters.
129(26), 268101.
mla: Meadowcroft, Billie, et al. “Mechanochemical Rules for Shape-Shifting Filaments
That Remodel Membranes.” Physical Review Letters, vol. 129, no. 26, 268101,
American Physical Society, 2022, doi:10.1103/PhysRevLett.129.268101.
short: B. Meadowcroft, I. Palaia, A.K. Pfitzner, A. Roux, B. Baum, A. Šarić, Physical
Review Letters 129 (2022).
date_created: 2023-01-08T23:00:53Z
date_published: 2022-12-23T00:00:00Z
date_updated: 2023-08-03T14:10:59Z
day: '23'
department:
- _id: AnSa
doi: 10.1103/PhysRevLett.129.268101
ec_funded: 1
external_id:
isi:
- '000906721500001'
pmid:
- '36608212'
intvolume: ' 129'
isi: 1
issue: '26'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2022.05.10.490642 '
month: '12'
oa: 1
oa_version: Preprint
pmid: 1
project:
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
call_identifier: H2020
grant_number: '101034413'
name: 'IST-BRIDGE: International postdoctoral program'
- _id: eba2549b-77a9-11ec-83b8-a81e493eae4e
call_identifier: H2020
grant_number: '802960'
name: 'Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines'
- _id: eba0f67c-77a9-11ec-83b8-cc8501b3e222
grant_number: '96752'
name: 'The evolution of trafficking: from archaea to eukaryotes'
publication: Physical Review Letters
publication_identifier:
eissn:
- 1079-7114
issn:
- 0031-9007
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanochemical rules for shape-shifting filaments that remodel membranes
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 129
year: '2022'
...