Journal article
Spatial Deconstruction of the Plasma Membrane
Journal of the American Chemical Society
08/04/2026
DOI: 10.1021/jacs.6c10688
Abstract
The plasma membrane of cells is known to be heterogeneous with regard to the spatial distribution of proteins and lipids, but the nature and origins of this heterogeneity are unclear. In this study, we perform fluorescence microscopy on plasma membrane sheets and find that most proteins occur in protein-rich domains separated by intervening protein-poor regions. We show that the protein-rich domains and protein-poor regions are at least partially preserved in plasma membrane-derived vesicles that lack cytoskeletal elements, permitting their separation and isolation by density centrifugation. Compositional analysis by nuclear magnetic resonance and mass spectrometry shows that different proteins and lipids exhibit distinct tendencies to partition into the protein-rich domains. This differential partitioning is correlated with the function of the different proteins, suggesting segregation based on cellular processes. Likewise, ordered lipids, including cholesterol and sphingomyelin, differentially segregate, being more abundant in the protein-rich domains. We propose that the collective assembly of certain proteins and lipids creates the heterogeneous distribution of membrane components and the emergence of protein-rich domains. These domains could create distinct environments for the function and segregation of various membrane processes.
Details
- Title: Subtitle
- Spatial Deconstruction of the Plasma Membrane
- Creators
- Venkata Shiva Mandala - University of IowaChen Zhao - University of FloridaQiuying Chen - Cornell UniversitySteven Gross - Cornell UniversityJacob Geri - Cornell UniversityRoderick MacKinnon - Rockefeller University
- Resource Type
- Journal article
- Publication Details
- Journal of the American Chemical Society
- DOI
- 10.1021/jacs.6c10688
- ISSN
- 0002-7863
- eISSN
- 1520-5126
- Publisher
- American Chemical Society
- Grant note
- Howard Hughes Medical Institute: NA Jane Coffin Childs Memorial Fund for Medical Research: NA
We thank Priyam Banerjee, Alison North, and other members of the Bio-Imaging Resource Center for their assistance with fluorescence imaging experiments. We thank Johanna Sotiris, Honkit Ng, and Mark Ebrahim at the Evelyn Gruss Lipper Cryo-EM Resource Center for assistance with cryo-EM grid screening. We thank Sean Brady for providing access to the NMR spectrometer and Yi Chun Hsiung for assistance with insect and mammalian cell cultures. Finally, we thank members of the MacKinnon Lab for helpful discussions and Dr. Jue Chen and her research group for their advice. V.S.M. is supported by the Jane Coffin Childs Memorial Fund Fellowship. R.M. is an investigator at the Howard Hughes Medical Institute.
- Language
- English
- Electronic publication date
- 08/04/2026
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9985216948402771
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