Supported Lipid Bilayers for Atomic Force Microscopy Studies

Lv, Zhengjian; Banerjee, Siddhartha; Zagorski, Karen; Lyubchenko, Yuri L.

doi:10.1007/978-1-4939-8591-3_8

Cited by 34 publications

(40 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another interest in the interaction of Aβ proteins with membranes was the elevated rate of assembly of aggregates-primarily fibrils [30,31]; however, the role of membranes in the assembly of oligomers remains unexplored. We have recently discovered a novel property of surfaces, including phospholipid bilayers, in which surface plays the role of a catalyst enabling the assembly of oligomers to occur at nanomolar concentrations [19][20][21][22]. This finding is of great importance, as concentrations of Aβ proteins in vivo are in the low nanomolar concentration range.…”

Section: Discussionmentioning

confidence: 99%

“…Freshly cleaved mica was used as the support substrate. We developed a method which is described in papers [19,20,22,26]. Typical examples of AFM images of POPC, POPS and POPC:POPS bilayers are shown in Figure S1.…”

Section: Aggregation On Supported Lipid Bilayers (Slb)mentioning

confidence: 99%

“…We have recently examined whether the surface catalysis process can be extended to membrane surfaces. We selected α-synuclein (α-syn) and performed time-lapse AFM studies [20,22]. We used supported lipid bilayers (SLBs) formed by 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS), which are major components of neuronal membranes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interaction of Aβ42 with Membranes Triggers the Self-Assembly into Oligomers

Banerjee

Hashemi

Zagorski

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

The self-assembly of amyloid β (Aβ) proteins into oligomers is the major pathogenic event leading to Alzheimer’s disease (AD). Typical in vitro experiments require high protein concentrations, whereas the physiological concentration of Aβ is in the picomolar to low nanomolar range. This complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here, we demonstrate that Aβ42 self-assembles into aggregates on membrane bilayers at low nanomolar concentrations - a pathway in which the membrane plays the role of a catalyst. Additionally, physiological ionic conditions (150 mM NaCl) significantly enhance on-membrane aggregation, leading to the rapid formation of oligomers. The self-assembly process is reversible, so assembled aggregates can dissociate from the membrane surface into the bulk solution to further participate in the aggregation process. Molecular dynamics simulations demonstrate that the transient membrane-Aβ interaction dramatically changes the protein conformation, facilitating the assembly of dimers. The results indicate peptide–membrane interaction is the critical step towards oligomer formation at physiologically low protein concentrations.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Aggregation On Supported Lipid Bilayers (Slb)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interaction of Aβ42 with Membranes Triggers the Self-Assembly into Oligomers

Banerjee

Hashemi

Zagorski

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…We used time-lapse AFM to directly visualize the aggregation process of Aβ42 protein on supported lipid bilayers formed from 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS) using the approaches described in [10][11][12][13] . A solution of 10 nM Aβ42 was placed on top of the SLBs, assembled on the mica substrate, and imaged at room temperature.…”

Section: Resultsmentioning

confidence: 99%

“…SLBs assembled from POPC, POPS, and 1:1 (mol) mixture of POPC:POPS were used. Assembly of SLB with smooth surface topography that remains stable during hours of observation is critical in these studies and we used methodology recently developed in the lab 11,12 . Typical examples of AFM images of POPC, POPS and POPC:POPS bilayers are shown in Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Lipid membranes trigger misfolding and self-assembly of amyloid β 42 protein into aggregates

Banerjee

Hashemi

Zagorski

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

The assembly of polypeptides and proteins into nanoscale aggregates is a phenomenon observed in a vast majority of proteins. Importantly, aggregation of amyloid β (Aβ) proteins is considered as a major cause for the development of Alzheimer's disease. The process depends on various conditions and typical test-tube experiments require high protein concentration that complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here we demonstrate that Aβ42 monomers at the membrane bilayer are capable of self-assembling into aggregates at physiologically low concentrations, and the membrane in this aggregation process plays a role of a catalyst. We applied all-atom molecular dynamics to demonstrate that the interaction with the membrane surface dramatically changes the conformation of Aβ42 protein. As a result, the misfolded Aβ42 rapidly assembles into dimers, trimers and tetramers, so the on-surface aggregation is the mechanism by which amyloid oligomers are produced and spread.Self-assembly is a widely spread phenomenon in biology and the assembly of proteins into nanoaggerates with various morphologies is a phenomenon of a special attention for decades. Evidence strongly suggests that the development of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), is due to the self-assembly of amyloid β (Aβ) and α-synuclein oligomers, respectively 1 . These oligomers appear to disrupt the cell homeostasis, by various mechanisms, resulting in the early stages of neurodegenerative diseases 2-4 . The amyloid cascade hypothesis (ACH) 5 is the major model that describes the pathology of AD and other neurodegenerative diseases 5-9 . However, several orders higher concentrations of Aβ compared with that found in vivo are required for the spontaneous aggregation of Aβ, which challenges the validity of ACH. We have discovered that amyloid proteins and peptides are capable of assembling into aggregates at nanomolar concentration range if the process occurs at the surface-liquid interface 10,11 . In the present study, we monitored the aggregation of Aβ42 at its physiologically relevant low concentration (10 nM) on supported lipid bilayers (SLBs) formed by 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-snglycero-3-phospho-L-serine (POPS).Direct time-lapse AFM imaging revealed Aβ42 aggregation on the bilayer surfaces, while no self-assembly of Aβ42 was detected in bulk solution. We performed computational modeling of the aggregation process on the membrane surfaces to demonstrate that interaction of Aβ42 dramatically changes the conformation of Aβ42 monomers. Moreover, membrane-bound Aβ42 proteins trigger the assembly of dimers, trimers, and tetramers, propagating the misfolded states of the Aβ42 molecules. Thus, interaction with membranes results in the transition of Aβ42 into the aggregation-prone, misfolded conformations. Such conformations have not been reported in

show abstract

Caught in Action: Visualizing Dynamic Nanostructures Within Supramolecular Systems Chemistry

et al. 2022

View full text Add to dashboard Cite

Supramolecular systems chemistry has been an area of active research to develop nanomaterials with life-like functions. Progress in systems chemistry relies on our ability to probe the nanostructure formation in solution. Often visualizing the dynamics of nanostructures which transform over time is a formidable challenge. This necessitates a paradigm shift from dry sample imaging towards solution-based techniques. We review the application of state-of-the-art techniques for real-time, in situ visualization of dynamic self-assembly processes. We present how solution-based techniques namely optical super-resolution microscopy, solution-state atomic force microscopy, liquid-phase transmission electron microscopy, molecular dynamics simulations and other emerging techniques are revolutionizing our understanding of active and adaptive nanomaterials with life-like functions. This Review provides the visualization toolbox and futuristic vision to tap the potential of dynamic nanomaterials.

show abstract

Supported Lipid Bilayers for Atomic Force Microscopy Studies

Cited by 34 publications

References 14 publications

Interaction of Aβ42 with Membranes Triggers the Self-Assembly into Oligomers

Interaction of Aβ42 with Membranes Triggers the Self-Assembly into Oligomers

Lipid membranes trigger misfolding and self-assembly of amyloid β 42 protein into aggregates

Caught in Action: Visualizing Dynamic Nanostructures Within Supramolecular Systems Chemistry

Contact Info

Product

Resources

About