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A synthetic amyloid lawn system for high-throughput analysis of amyloid toxicity and drug screening
- Source :
- Biomaterials. 29:2813-2819
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Amyloid-beta (Abeta) is the major constituent of senile plaques in the brains of Alzheimer's disease patients. In order to develop an efficient in vitro system for studying the interaction of cells with Abeta aggregates, we have prepared a synthetic amyloid lawn by immobilizing Abeta peptides over a functionalized glass surface and subsequently incubating the template in a fresh Abeta solution. On the top of different types of amyloid lawns (e.g. monomeric, oligomeric, and fibrillar), we cultivated PC12 cells, creating physical contacts between the cells and the lawns. Results indicated that cell viability was differentially affected when grown atop different Abeta lawns while cells were well adhered onto the surface of these Abeta lawns. The mode of cell death by Abeta lawn was confirmed to be apoptotic rather than necrotic, showing that cells undergo suicide by just contact with Abeta lawn. While conventional 'solution-based' methods for testing amyloid toxicity suffer from problems such as lot-to-lot variations, continued fibrillation, and heterogeneous population of aggregates, our 'surface-based' lawn system is suitable for high-throughput analysis of amyloid toxicity, which may enable high-throughput screening of potential drug candidates for treating amyloid diseases with the goal of reducing the cell death on the lawn.
- Subjects :
- Pathology
medicine.medical_specialty
Programmed cell death
Amyloid
Cell Survival
Drug Evaluation, Preclinical
Biophysics
Apoptosis
Bioengineering
Biology
Microscopy, Atomic Force
PC12 Cells
Biomaterials
Amyloid disease
mental disorders
medicine
Animals
Senile plaques
Viability assay
Amyloid beta-Peptides
P3 peptide
Rats
Microscopy, Fluorescence
Biochemistry
Mechanics of Materials
Caspases
Toxicity
Ceramics and Composites
Subjects
Details
- ISSN :
- 01429612
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Biomaterials
- Accession number :
- edsair.doi.dedup.....3fdbb65ed4bd1b9a1eb2fcca910b2e9f