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The role of shear f...
The role of shear forces in primary and secondary nucleation of amyloid fibrils
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- Axell, Emil (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
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- Hu, Jing (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Fysikalisk kemi,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Physical Chemistry,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
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- Lindberg, Max (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
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- Dear, Alexander J. (författare)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,University of Cambridge
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- Ortigosa-Pascual, Lei (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
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- Andrzejewska, Ewa A. (författare)
- University of Cambridge
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- Šneiderienė, Greta (författare)
- University of Cambridge
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- Thacker, Dev (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
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- Knowles, Tuomas P. J. (författare)
- University of Cambridge
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- Sparr, Emma (författare)
- Lund University,Lunds universitet,Fysikalisk kemi,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Physical Chemistry,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LU Profile Area: Proactive Ageing,Lund University Profile areas
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- Linse, Sara (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,LU profilområde: Proaktivt åldrande,Other operations, LTH,Faculty of Engineering, LTH,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas,LU Profile Area: Proactive Ageing
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(creator_code:org_t)
- 2024
- 2024
- Engelska 10 s.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 121:25, s. 2322572121-2322572121
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Shear forces affect self-assembly processes ranging from crystallization to fiber formation. Here, the effect of mild agitation on amyloid fibril formation was explored for four peptides and investigated in detail for Aβ42, which is associated with Alzheimer's disease. To gain mechanistic insights into the effect of mild agitation, nonseeded and seeded aggregation reactions were set up at various peptide concentrations with and without an inhibitor. First, an effect on fibril fragmentation was excluded by comparing the monomer-concentration dependence of aggregation kinetics under idle and agitated conditions. Second, using a secondary nucleation inhibitor, Brichos, the agitation effect on primary nucleation was decoupled from secondary nucleation. Third, an effect on secondary nucleation was established in the absence of inhibitor. Fourth, an effect on elongation was excluded by comparing the seeding potency of fibrils formed under idle or agitated conditions. We find that both primary and secondary nucleation steps are accelerated by gentle agitation. The increased shear forces facilitate both the detachment of newly formed aggregates from catalytic surfaces and the rate at which molecules are transported in the bulk solution to encounter nucleation sites on the fibril and other surfaces. Ultrastructural evidence obtained with cryogenic transmission electron microscopy and free-flow electrophoresis in microfluidics devices imply that agitation speeds up the detachment of nucleated species from the fibril surface. Our findings shed light on the aggregation mechanism and the role of detachment for efficient secondary nucleation. The results inform on how to modulate the relative importance of different microscopic steps in drug discovery and investigations.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Amyloid/metabolism
- Kinetics
- Humans
- Shear Strength
- Protein Aggregates
- Peptides/chemistry
- Alzheimer Disease/metabolism
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Till lärosätets databas
- Av författaren/redakt...
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Axell, Emil
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Hu, Jing
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Lindberg, Max
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Dear, Alexander ...
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Ortigosa-Pascual ...
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Andrzejewska, Ew ...
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visa fler...
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Šneiderienė, Gre ...
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Thacker, Dev
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Knowles, Tuomas ...
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Sparr, Emma
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Linse, Sara
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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Lunds universitet