scholarly journals Kinetics of small molecule interactions with membrane proteins in single cells measured with mechanical amplification

2015 ◽  
Vol 1 (9) ◽  
pp. e1500633 ◽  
Author(s):  
Yan Guan ◽  
Xiaonan Shan ◽  
Fenni Zhang ◽  
Shaopeng Wang ◽  
Hong-Yuan Chen ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Small Molecule ◽  
Single Cells ◽  
Cellular Membrane ◽  
Mechanical Amplification ◽  
New Strategy ◽  
Interaction Kinetics ◽  
Molecule Interactions ◽  
Difficult Challenge ◽  
Membrane Protein Interaction

Measuring small molecule interactions with membrane proteins in single cells is critical for understanding many cellular processes and for screening drugs. However, developing such a capability has been a difficult challenge. We show that molecular interactions with membrane proteins induce a mechanical deformation in the cellular membrane, and real-time monitoring of the deformation with subnanometer resolution allows quantitative analysis of small molecule–membrane protein interaction kinetics in single cells. This new strategy provides mechanical amplification of small binding signals, making it possible to detect small molecule interactions with membrane proteins. This capability, together with spatial resolution, also allows the study of the heterogeneous nature of cells by analyzing the interaction kinetics variability between different cells and between different regions of a single cell.

scholarly journals The cellular membrane as a mediator for small molecule interaction with membrane proteins

2016 ◽  
Vol 1858 (10) ◽  
pp. 2290-2304 ◽  
Author(s):  
Christopher G. Mayne ◽  
Mark J. Arcario ◽  
Paween Mahinthichaichan ◽  
Javier L. Baylon ◽  
Josh V. Vermaas ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Small Molecule ◽  
Cellular Membrane ◽  
Molecule Interaction

Small Molecule Interactions with Protein−Tyrosine Phosphatase PTP1B and Their Use in Inhibitor Design†

Biochemistry ◽  
1996 ◽  
Vol 35 (50) ◽  
pp. 15989-15996 ◽  
Author(s):  
Terrence R. Burke, ◽  
Bin Ye ◽  
Xinjian Yan ◽  
Shaomeng Wang ◽  
Zongchao Jia ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Inhibitor Design ◽  
Protein Tyrosine ◽  
Molecule Interactions

scholarly journals Identification of a Hydrophobic Cleft in the LytTR Domain of AgrA as a Locus for Small Molecule Interactions That Inhibit DNA Binding

Biochemistry ◽  
2012 ◽  
Vol 51 (50) ◽  
pp. 10035-10043 ◽  
Author(s):  
Paul G. Leonard ◽  
Ian F. Bezar ◽  
David J. Sidote ◽  
Ann M. Stock
Keyword(s):  
Dna Binding ◽  
Small Molecule ◽  
Molecule Interactions ◽  
Hydrophobic Cleft

scholarly journals A small molecule screen identified N-Acetyl-L-cysteine for promoting ex vivo growth of single circulating tumor cells

2020 ◽  
Author(s):  
Teng Teng ◽  
Mohamed Kamal ◽  
Oihana Iriondo ◽  
Yonatan Amzaleg ◽  
Chunqiao Luo ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Small Molecule ◽  
Ex Vivo ◽  
Single Cells ◽  
Small Subset ◽  
Blood Draw ◽  
Small Molecule Screen ◽  
Functional Analyses ◽  
Single Ctcs

AbstractCirculating tumor cells (CTCs) can be isolated via a minimally invasive blood draw and are considered a “liquid biopsy” of their originating solid tumors. CTCs contain a small subset of metastatic precursors that can form metastases in secondary organs, and provide a resource to identify mechanisms underlying metastasis-initiating properties. Despite technological advancements that allow for highly sensitive approaches of detection and isolation, CTCs are very rare and often present as single cells, posing an extreme challenge for ex vivo expansion after isolation. Here, using previously established patient-derived CTC lines, we performed a small molecule drug screening to identify compounds that can improve ex vivo culture efficiency for single CTCs. We found that N-acetylcysteine (NAC) and other antioxidants can promote ex vivo expansion of single CTCs, by reducing oxidative and other stress particularly at the initial stage of single cell expansion. RNA-seq analysis of growing clones and non-growing clones confirmed the effect by NAC, but also indicate that NAC-induced decrease in oxidative stress is insufficient for promoting proliferation of a subset of cells with heterogeneous quiescent and senescent features. Despite the challenge in expanding all CTCs, NAC treatment lead to establishment of single CTC clones that have similar tumorigenic features, which will facilitate future functional analyses.

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