High-resolution label-free 3D mapping of extracellular pH of single living cells

Abstract

Dynamic mapping of extracellular pH (pHe) at the single-cell level is critical for understanding the role of H+ in cellular and subcellular processes, with particular importance in cancer. While several pHe sensing techniques have been developed, accessing this information at the single-cell level requires improvement in sensitivity, spatial and temporal resolution. We report on a zwitterionic label-free pH nanoprobe that addresses these long-standing challenges. The probe has a sensitivity > 0.01 units, 2 ms response time, and 50 nm spatial resolution. The platform was integrated into a double-barrel nanoprobe combining pH sensing with feedback-controlled distance dependance via Scanning Ion Conductance Microscopy. This allows for the simultaneous 3D topographical imaging and pHe monitoring of living cancer cells. These classes of nanoprobes were used for real-time high spatiotemporal resolution pHe mapping at the subcellular level and revealed tumour heterogeneity of the peri-cellular environments of melanoma and breast cancer cells.

Unravelling Metal Speciation in the Microenvironment Surrounding Phytoplankton Cells to Improve Predictions of Metal Bioavailability

“…The data sources include a diversity of taxonomic groups including green algae, diatoms, cyanobacteria, chromista algae, and yellow-green algae from freshwater or marine environments, and the size of these species ranges from a few micrometers (e.g., Thalassiosira weissflogii ) 20 to hundreds of micrometers (e.g., Coscinodiscus wailesii ( 9 , 10 ) and Odontella sinensis ( 8 )). The studied samples include individual cells 8 , 9 , 20 and cell aggregates/colonies.…”

“… 8 , 21 Some studies employed fluorescence pH dyes 20 or monitored pH sensitive extracellular reactions, 22 and one recent work used a novel pH nanoprobe. 10 Concentration gradients of both pH and O 2 in the phycosphere were reported for cell aggregates/colonies in some studies, but the data are rare for microalgae simply due to technical limitations in spatial resolution. The data we compiled in Figure 1 were those measured within the phycosphere, but the exact distances of the measurement points from the cell membrane are unknown.…”

Novel T7-modified pH-responsive targeted nanosystem for co-delivery of docetaxel and curcumin in the treatment of esophageal cancer

“…Stimuli-responsive release of nanomedicines is based on the specific microenvironment of tumor tissue, which not only enables maximum release of drug into tumor tissue, but also reduces damage to normal tissue [31] 1 . Herein, we tested the drug-release efficiency of the nanomedicines in a simulated tumor microenvironment.…”

Scanning ion conductance microscopy of isolated metaphase chromosomes in a liquid environment

“…Its biological application was thus first reported by Korchev et al (1997), who observed live cultured cells under liquid conditions. Since then, SICM has been used to obtain images of the surface information of different cultured cells (Korchev et al 2000;Pastré et al 2001;Happel et al 2003;Gorelik et al 2004;Gorelik et al 2006;Chen et al 2013;McKelvey et al 2014;Zhou et al 2016Zhou et al , 2017Simeonov and Schaffer 2019;Zhang et al 2019;Takahashi et al 2020).…”