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Observation of α-Synuclein Preformed Fibrils Interacting with SH-SY5Y Neuroblastoma Cell Membranes Using Scanning Ion Conductance Microscopy

Feng, Christina and Flores, Marisol and Dhoj, Christina and Garcia, Adaly and Belleca, Sheehan and Abbas, Dana Abou and Parres-Gold, Jacob and Anguiano, Aimee and Porter, Edith and Wang, Yixian (2022) Observation of α-Synuclein Preformed Fibrils Interacting with SH-SY5Y Neuroblastoma Cell Membranes Using Scanning Ion Conductance Microscopy. ACS Chemical Neuroscience, 13 (24). pp. 3547-3553. ISSN 1948-7193. PMCID PMC9782390. doi:10.1021/acschemneuro.2c00478.

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Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder in the U.S. α-Synuclein (α-Syn) preformed fibrils (PFFs) have been shown to propagate PD pathology in neuronal populations. However, little work has directly characterized the morphological changes on membranes associated with α-Syn PFFs at a cellular level. Scanning ion conductance microscopy (SICM) is a noninvasive in situ cell imaging technique and therefore uniquely advantageous to investigate PFF-induced membrane changes in neuroblastoma cells. The present work used SICM to monitor cytoplasmic membrane changes of SH-SY5Y neuroblastoma cells after incubation with varying concentrations of α-Syn PFFs. Cell membrane roughness significantly increased as the concentration of α-Syn PFFs increased. Noticeable protrusions that assumed a more crystalline appearance at higher α-Syn PFF concentrations were also observed. Cell viability was only slightly reduced, though statistically significantly, to about 80% but independent of the dose. These observations indicate that within the 48 h treatment period, PFFs continue to accumulate on the cell membranes, leading to membrane roughness increase without causing prominent cell death. Since PFFs did not induce major cell death, these data suggest that early interventions targeting fibrils before further aggregation may prevent the progression of neuron loss in Parkinson’s disease.

Item Type:Article
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URLURL TypeDescription CentralArticle
Parres-Gold, Jacob0000-0002-2050-0139
Porter, Edith0000-0002-4656-5264
Wang, Yixian0000-0001-8691-1128
Additional Information:Prof. Jamil Momand (California State University, Los Angeles) and his student Lizbeth Flores are greatly appreciated for assisting with cell culturing. Prof. Shannon Boettcher (University of Oregon) and his student Nick D’Antona are greatly appreciated for the SEM characterization of the nanopipettes. This work was supported by the NIH R15 (Grant 1R15NS120157-01) and the CSUPERB Presidents’ Commission Scholars Program. S.B. was the recipient of the California State University, Los Angeles, MARC USTAR program (Grant NIH T34GM08228), and A.A. was the recipient of a CREST-CATSUS fellowship (Grant NSF HRD-2112554). We also appreciate the facility support from the NSF Award HRD-1547723.
Funding AgencyGrant Number
California State University, Los AngelesUNSPECIFIED
NIH Predcotoral FellowshipT34GM08228
Issue or Number:24
PubMed Central ID:PMC9782390
Record Number:CaltechAUTHORS:20221219-418113000.45
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:118514
Deposited By: Research Services Depository
Deposited On:25 Jan 2023 15:39
Last Modified:25 Jan 2023 18:36

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