Journal
BIOPHYSICAL JOURNAL
Volume 98, Issue 8, Pages 1703-1711Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2009.12.4289
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Funding
- Leverhulme Trust
- Rothermere Trust Foundation
- National Science and Engineering Research Council (Canada)
- Canadian Centennial Scholarship Fund
- Department of Health (United Kingdom)
- National Institute for Health Research Respiratory Disease Biomedical Research Unit at the Royal Brompton
- National Health Service Foundation Trust
- Imperial College London
- Medical Research Council [G0700926, G0801056B] Funding Source: researchfish
- MRC [G0700926] Funding Source: UKRI
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Researchers have previously questioned the suitability of cell lines as models for primary cells. In this study, we used Raman microspectroscopy to characterize live A549 cells from a unique molecular biochemical perspective to shed light on their suitability as a model for primary human pulmonary alveolar type II (ATII) cells. We also investigated a recently developed transduced type I (TT1) cell line as a model for alveolar type I (ATI) cells. Single-cell Raman spectra provide unique biomolecular fingerprints that can be used to characterize cellular phenotypes. A multivariate statistical analysis of Raman spectra indicated that the spectra of A549 and TT1 cells are characterized by significantly lower phospholipid content compared to ATII and ATI spectra because their cytoplasm contains fewer surfactant lamellar bodies. Furthermore, we found that A549 spectra are statistically more similar to ATI spectra than to ATII spectra. The spectral variation permitted phenotypic classification of cells based on Raman spectral signatures with >99% accuracy. These results suggest that A549 cells are not a good model for ATII cells, but TT1 cells do provide a reasonable model for ATI cells. The findings have far-reaching implications for the assessment of cell lines as suitable primary cellular models in live cultures.
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