Human islet amyloid polypeptide at the air–aqueous interface: a Langmuir monolayer approach

Li, Shanghao; Mićić, Miodrag; Orbulescu, Jhony; Whyte, Jeffrey D.; Leblanc, Roger M.

doi:10.1098/rsif.2012.0368

Cited by 26 publications

(33 citation statements)

References 72 publications

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“…Comparable to amphipathic AMPs, amyloid proteins show a strong binding preference to lipid membranes at a μM range (Matsuzaki, 2007; Galvagnion et al ., 2015). This binding results in packing defects and increases the surface pressure in lipid membranes (Li et al ., 2012; Chaari et al ., 2013). For instance, the thinning of the outer acyl chain layer of lipid membranes has been observed in the presence of α -syn, IAPP and A β (Hebda and Miranker, 2009; Hellstrand et al ., 2013; Li et al ., 2016; Korshavn et al ., 2017).…”

Section: Contributions To the Understanding Of Amyloid Toxicity In LImentioning

confidence: 99%

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Cao

Loch

et al. 2020

Quart. Rev. Biophys.

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In neurodegenerative diseases, a wide range of amyloid proteins or peptides such as amyloid-beta and α-synuclein fail to keep native functional conformations, followed by misfolding and self-assembling into a diverse array of aggregates. The aggregates further exert toxicity leading to the dysfunction, degeneration and loss of cells in the affected organs. Due to the disordered structure of the amyloid proteins, endogenous molecules, such as lipids, are prone to interact with amyloid proteins at a low concentration and influence amyloid cytotoxicity. The heterogeneity of amyloid proteinscomplicates the understanding of the amyloid cytotoxicity when relying only on conventional bulk and ensemble techniques. As complementary tools, single-molecule techniques (SMTs) provide novel insights into the different subpopulations of a heterogeneous amyloid mixture as well as the cytotoxicity, in particular as involved in lipid membranes. This review focuses on the recent advances of a series of SMTs, including single-molecule fluorescence imaging, single-molecule force spectroscopy and single-nanopore electrical recording, for the understanding of the amyloid molecular mechanism. The working principles, benefits and limitations of each technique are discussed and compared in amyloid protein related studies.. We also discuss why SMTs show great potential and are worthy of further investigation with feasibility studies as diagnostic tools of neurodegenerative diseases and which limitations are to be addressed.

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Section: Contributions To the Understanding Of Amyloid Toxicity In LImentioning

confidence: 99%

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Cao

Loch

et al. 2020

Quart. Rev. Biophys.

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“…As the Ficoll meshwok expands at the AWI, it would compress the IAPP network leading to an increase in IAPP molecular packing. An increase of the number of IAPP molecules per unit area by compression of a Langmuir monolayer was previously demonstrated [ 64 ]. This increase in effective IAPP concentration in localised AWI areas would accelerate not only the already fast maturation of IAPP droplets, but also aggregation from the droplet surface, formation of aggregate clusters, and therefore the onset of cluster fusion.…”

Section: Discussionmentioning

confidence: 99%

The kinetics of islet amyloid polypeptide phase-separated system and hydrogel formation are critically influenced by macromolecular crowding

Pytowski

Vaux

Jean

2021

Biochemical Journal

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Many protein misfolding diseases (e.g. type II diabetes and Alzheimer’s disease) are characterised by amyloid deposition. Human islet amyloid polypeptide (hIAPP, involved in type II diabetes) spontaneously undergoes liquid-liquid phase separation (LLPS) and a kinetically complex hydrogelation, both catalysed by hydrophobic-hydrophilic interfaces (e.g. air-water interface and/or phospholipids-water interfaces). Gelation of hIAPP phase separated liquid droplets initiates amyloid aggregation and formation of clusters of interconnected aggregates, which grow and fuse to eventually percolate the whole system. Droplet maturation into irreversible hydrogels via amyloid aggregation is thought to be behind the pathology of several diseases. Biological fluids contain a high volume fraction of macromolecules, leading to macromolecular crowding. Despite crowding agent addition in in vitro studies playing a significant role in changing protein phase diagrams, the mechanism underlying enhanced LLPS, and the effect(s) on stages beyond LLPS remain poorly or not characterised.  We investigated the effect of macromolecular crowding and increased viscosity on the kinetics of hIAPP hydrogelation using rheology and the evolution of the system beyond LLPS by microscopy. We demonstrate that increased viscosity exacerbated the kinetic variability of hydrogelation and of the phase separated-aggregated system, whereas macromolecular crowding abolished heterogeneity. Increased viscosity also strengthened the gel meshwork and accelerated aggregate cluster fusion. In contrast, crowding either delayed cluster fusion onset (dextran) or promoted it (Ficoll). Our study highlights that an in vivo crowded environment would critically influence amyloid stages beyond LLPS and pathogenesis.

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“…IAPP pathological aggregation is enhanced by peptide concentration, pH, and temperature variation above and below critical thresholds [23]. The aggregation of insulin has taken place due to the direct interaction and copolymerization between insulin and hIAPP [24]. Both IAPP and insulin have enough opportunity to interact due to sharing the same secretory pathway in the β-cells.…”

Section: Introductionmentioning

confidence: 99%

In Silico Studies of The Human IAPP In Presence of Osmolytes

Khan

Jahan

Nayeem

2021

Preprint

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The human islet amyloid polypeptide or amylin is secreted along with insulin by pancreatic islets. Under the drastic environmental conditions, amylin can aggregate to form amyloid fibrils. This amyloid plaque of hIAPP in the pancreatic cells is the cause of Type II diabetes. Early stages of amylin aggregates are more cytotoxic than the matured fibrils. Here, we have used the all-atom molecular dynamic simulation to see the effect of water, TMAO, urea and urea:TMAO having ratio 2:1 of different concentrations on the amylin protein. Our study suggest that the amylin protein forms β-sheets in its monomeric form and may cause the aggregation of protein through the residue 13-17 and the C-terminal region. α-helical content of protein increases with an increase in TMAO concentration by decreasing the SASA value of protein, increase in intramolecular hydrogen bonds and on making the short range hydrophobic interactions. Electrostatic potential surfaces shows that hydrophobic groups are buried and configurational entropy of backbone atoms is lesser in presence of TMAO, whereas opposite behaviour is obtained in case of urea. Counteraction effect of TMAO using Kast model towards urea is also observed in ternary solution of urea:TMAO.

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Human islet amyloid polypeptide at the air–aqueous interface: a Langmuir monolayer approach

Cited by 26 publications

References 72 publications

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

The kinetics of islet amyloid polypeptide phase-separated system and hydrogel formation are critically influenced by macromolecular crowding

In Silico Studies of The Human IAPP In Presence of Osmolytes

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