PMID- 36228282
OWN - NLM
STAT- MEDLINE
DCOM- 20221122
LR  - 20230124
IS  - 2576-6422 (Electronic)
IS  - 2576-6422 (Linking)
VI  - 5
IP  - 11
DP  - 2022 Nov 21
TI  - Following the Aggregation of Human Prion Protein on Heparin Functionalized Gold 
      Surface in Real Time.
PG  - 5457-5464
LID - 10.1021/acsabm.2c00779 [doi]
AB  - The aggregation of the prion protein (PrP) plays a key role in the development of 
      prion diseases and is believed to be an autocatalytic process with a very high 
      kinetic barrier. Intensive studies have focused on overcoming the kinetic 
      barriers under extremely nonphysiological in vitro conditions by altering the pH 
      of PrP solution on solid surfaces, such as gold, mica, and a lipid bilayer. 
      Importantly, sulfated glycosaminoglycans (GAGs), including heparin, were found to 
      be associated with PrP misfolding and aggregation, suggesting GAGs have catalytic 
      roles in PrP aggregation processes. However, the exact role and details of GAGs 
      in the PrP aggregation are not clear and need a thorough perusal. Here, we 
      investigate the PrP aggregation process on a heparin functionalized gold surface 
      by in situ, real-time monitoring of the atomic scale details of the whole 
      aggregation process by single molecule atomic force microscopy (AFM), combining 
      simultaneous topographic and recognition (TREC) imaging and single molecule force 
      spectroscopy (SMFS). We observed the whole aggregation process for full-length 
      human recombinant PrP (23-231) aggregation on the heparin modified gold surface, 
      from the formation of oligomers, to the assembly of protofibrils and short 
      fibers, and the formation of elongated mature fibers. Heparin is found to promote 
      the PrP aggregation by facilitating the formation of oligomers during the early 
      nucleation stage.
FAU - Zhang, Tong
AU  - Zhang T
AD  - Single Molecule Study Laboratory, College of Engineering and Nanoscale Science 
      and Engineering Center, University of Georgia, Athens, Georgia30602, United 
      States.
FAU - Pan, Yangang
AU  - Pan Y
AD  - Single Molecule Study Laboratory, College of Engineering and Nanoscale Science 
      and Engineering Center, University of Georgia, Athens, Georgia30602, United 
      States.
FAU - Kandapal, Sneha
AU  - Kandapal S
AUID- ORCID: 0000-0002-3572-1487
AD  - Single Molecule Study Laboratory, College of Engineering and Nanoscale Science 
      and Engineering Center, University of Georgia, Athens, Georgia30602, United 
      States.
FAU - Sun, Xin
AU  - Sun X
AUID- ORCID: 0000-0003-3153-8615
AD  - Single Molecule Study Laboratory, College of Engineering and Nanoscale Science 
      and Engineering Center, University of Georgia, Athens, Georgia30602, United 
      States.
FAU - Xu, Bingqian
AU  - Xu B
AUID- ORCID: 0000-0002-7873-3162
AD  - Single Molecule Study Laboratory, College of Engineering and Nanoscale Science 
      and Engineering Center, University of Georgia, Athens, Georgia30602, United 
      States.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20221013
PL  - United States
TA  - ACS Appl Bio Mater
JT  - ACS applied bio materials
JID - 101729147
RN  - 0 (Prions)
RN  - 0 (Prion Proteins)
RN  - 9005-49-6 (Heparin)
RN  - 7440-57-5 (Gold)
RN  - 0 (Glycosaminoglycans)
SB  - IM
MH  - Humans
MH  - *Prions/chemistry
MH  - Prion Proteins/chemistry
MH  - Heparin/chemistry
MH  - Gold
MH  - *Prion Diseases/metabolism
MH  - Glycosaminoglycans/metabolism
OTO - NOTNLM
OT  - PrP-heparin interaction
OT  - aggregation morphology
OT  - heparin
OT  - nucleation stage
OT  - prion protein (PrP) aggregation
EDAT- 2022/10/14 06:00
MHDA- 2022/11/23 06:00
CRDT- 2022/10/13 17:04
PHST- 2022/10/14 06:00 [pubmed]
PHST- 2022/11/23 06:00 [medline]
PHST- 2022/10/13 17:04 [entrez]
AID - 10.1021/acsabm.2c00779 [doi]
PST - ppublish
SO  - ACS Appl Bio Mater. 2022 Nov 21;5(11):5457-5464. doi: 10.1021/acsabm.2c00779. 
      Epub 2022 Oct 13.