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Probing Nanoscale Diffusional Heterogeneities in Cellular Membranes through Multidimensional Single-Molecule and
Rui Yan1,2, Kun Chen1,2, Ke Xu1,2
1Department of Chemistry, University of California, Berkeley, California 94720, United States.
Journal of the American Chemical Society
|October 21, 2020
Summary
Live cell membrane diffusion slows with increased lipid packing. Researchers mapped membrane topography and diffusivity, finding protein crowding, not lipid order, causes slowdowns at specific contact sites.
Area of Science:
- Biophysics
- Cell Biology
- Membrane Dynamics
Background:
- Biomembrane diffusion is crucial for cellular functions.
- Understanding nanoscale diffusion heterogeneity is key to cell biology.
Purpose of the Study:
- To concurrently map nanoscale membrane topography, diffusivity, and lipid packing order in live mammalian cells.
- To investigate the origins of diffusional heterogeneities in cellular membranes.
Main Methods:
- Developed a novel lipophilic fluorescence turn-on probe for sustained single-molecule imaging.
- Combined single-molecule imaging with super-resolution microscopy for nanoscale mapping.
- Utilized spectrally resolved single-molecule imaging to differentiate diffusion causes.
Main Results:
- Established a correlation between decreased membrane diffusivity and increased lipid packing order across different membrane regions (ER, plasma membrane, nanodomains).
- Discovered reduced diffusivity at endoplasmic reticulum-plasma membrane contact sites.
- Demonstrated that localized diffusion slowdown at contact sites is due to protein crowding, not altered lipid packing.
Conclusions:
- Integrated multidimensional single-molecule approach successfully maps nanoscale membrane properties.
- Differentiated nanoscale diffusional heterogeneities based on their origins (lipid packing vs. protein crowding).
- Provided new insights into the regulation of membrane dynamics at specific cellular locations.
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