Gold Nanoparticle-Based Surface-Enhanced Raman Scattering for Noninvasive Molecular Probing of Embryonic Stem Cell Differentiation

Abstract

This study reports the use of gold nanoparticle-based surface-enhanced Raman scattering (SERS) for probing the differentiation of mouse embryonic stem (mES) cells, including undifferentiated single cells, embryoid bodies (EBs), and terminally differentiated cardiomyocytes. Gold nanoparticles (GNPs) were successfully delivered into all 3 mES cell differentiation stages without affecting cell viability or proliferation. Transmission electron microscopy (TEM) confirmed the localization of GNPs inside the following cell organelles: mitochondria, secondary lysosome, and endoplasmic reticulum. Using bright- and dark-field imaging, the bright scattering of GNPs and nanoaggregates in all 3 ES cell differentiation stages could be visualized. EB (an early differentiation stage) and terminally differentiated cardiomyocytes both showed SERS peaks specific to metabolic activity in the mitochondria and to protein translation (amide I, amide II, and amide III peaks). These peaks have been rarely identified in undifferentiated single ES cells. Spatiotemporal changes observed in the SERS spectra from terminally differentiated cardiomyocyte tissues revealed local and dynamic molecular interactions as well as transformations during ES cell differentiation.

Laser-targeted photofabrication of gold nanoparticles inside cells

“…Quantitative assignment of peaks is always challenging in SERS analysis of an inhomogeneous sample, but a number of peaks appear at locations consistent with biological molecules. Peaks at 830, 1,295, 1,316, 1,438 and 1,444 cm À 1 are consistent with lipid components 20,21 , while 932, 968, 1,073, 1,159, 1,270 cm À 1 are commonly seen in protein (amide) or amino-acid bands 22,23 . Nucleic acids such as adenosine and guanosine are also readily detected by SERS and although often observed closer to 730 cm À 1 , the ring-breathing mode of adenosine is reported to undergo a shift, depending on the orientation to the SERS surface, and may be responsible for the strong peak around 749 cm À 1 (refs 24,25)…”

Raman spectroscopy: techniques and applications in the life sciences

“…A wide variety of cells and organelles have been studied using various modes of SERS such as lymphocytes [285], hemoglobin and other components of red blood cells [286], intracellular lipid compartments [287], mitochondria [288], stem cell differentiation into cardiomyocytes [289], differentiation of neuronal cells [290], and yeast cell wall spectroscopy [291] and imaging [291]. SERS particles functionalized with immunolabels have also been used to measure the external surface of endothelial cell membranes [292].…”

Reversing chemoresistance of malignant glioma stem cells using gold nanoparticles

“…Generally, gold nanoparticles have been reported to have good biocompatibility with nonstem cells, but with effects dependent upon the particular cell line used in the experiment. [32][33][34] Moreover, the surface chemistry, 35 size, 35 and concentration have been shown to affect the internalization mechanism for such nanomaterials. 36 The surface modifiers used to stabilize gold nanoparticles include a range of anionic, cationic, and neutral groups, such as citrate, amine, and glucose.…”