Long-term super-resolution inner mitochondrial membrane imaging with a lipid probe.
Shuai ZhengNeville DadinaDeepto MozumdarLauren LesiakKayli N MartinezEvan W MillerAlanna SchepartzPublished in: Nature chemical biology (2023)
The inner mitochondrial membrane (IMM) generates power to drive cell function, and its dynamics control mitochondrial health and cellular homeostasis. Here, we describe the cell-permeant, lipid-like small molecule MAO-N 3 and use it to assemble high-density environmentally sensitive (HIDE) probes that selectively label and image the IMM in live cells and multiple cell states. MAO-N 3 pairs with strain-promoted azide-alkyne click chemistry-reactive fluorophores to support HIDE imaging using confocal, structured illumination, single-molecule localization and stimulated emission depletion microscopy, all with significantly improved resistance to photobleaching. These probes generate images with excellent spatial and temporal resolution, require no genetic manipulations, are non-toxic in model cell lines and primary cardiomyocytes (even under conditions that amplify the effects of mitochondrial toxins) and can visualize mitochondrial dynamics for 12.5 h. This probe will enable comprehensive studies of IMM dynamics with high temporal and spatial resolution.
Keyphrases
- single molecule
- living cells
- small molecule
- oxidative stress
- high density
- high resolution
- atomic force microscopy
- induced apoptosis
- deep learning
- public health
- optical coherence tomography
- single cell
- healthcare
- cell therapy
- quantum dots
- mental health
- bone marrow
- high throughput
- climate change
- high speed
- endothelial cells
- photodynamic therapy
- fatty acid
- convolutional neural network
- protein protein
- signaling pathway
- solid state