Local Mechanical Perturbation Provides an Effective Means to Regulate the Growth and Assembly of Functional Peptide Fibrils.
Mucin 1 (MUC1) peptide fused with Q11 (MUC1-Q11) having 35 residues has previously been shown to form amyloid fibrils. Using time-dependent and high-resolution atomic force microscopy (AFM) imaging, it is revealed that the formation of individual MUC1-Q11 fibrils entails nucleation and extension at both ends. This process can be altered by local mechanical perturbations using AFM probes. This work reports two specific perturbations and outcomes. First, by increasing load while maintaining tip-surface contact, the fibrils are cut during the scan due to shearing. Growth of fibrils occurs at the newly exposed termini, following similar mechanism of the MUC1-Q11 nucleation growth. As a result, branched fibrils are seen on the surface whose orientation and length can be controlled by the nuclei orientation and reaction time. In contrast to the "one-time-cut", fibrils can be continuously fragmented by modulation at sufficiently high amplitude. As a result, short and highly branched fibrils accumulate and pile on surfaces. Since the fibril formation and assembly of MUC1-Q11 can be impacted by local mechanical force, this approach offers a nonchemical and label-free means to control the presentation of MUC1 epitopes, and has promising application in MUC1 fibril-based immunotherapy.
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Arpad
A
Karsai
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Teri Jo
TJ
Slack
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Hamed
H
Malekan
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Fadi
F
Khoury
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Wei-Feng
WF
Lin
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Victoria
V
Tran
Department of Physics, University of California, Davis, CA, 95616, USA.
Daniel
D
Cox
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Michael
M
Toney
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Xi
X
Chen
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Gang-Yu
GY
Liu
D000682:Amyloid / Q000737:chemistry; D018625:Microscopy, Atomic Force; D018396:Mucin-1 / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*
D000682:Amyloid; D018396:Mucin-1; D010455:Peptides
amyloid fibrils; atomic force microscopy; mechanical perturbation; mucin 1 peptides; nucleation; self-assembly