The diffusion rate of lipids in the cell membrane is reduced by a factor of 5–100 from that in artificial bilayers. This slowing mechanism has puzzled cell biologists for the last 25 yr. Here we address this issue by studying the movement of unsaturated phospholipids in rat kidney fibroblasts at the single molecule level at the temporal resolution of 25 μs. The cell membrane was found to be compartmentalized: phospholipids are confined within 230-nm-diameter (ϕ) compartments for 11 ms on average before hopping to adjacent compartments. These 230-nm compartments exist within greater 750-nm-ϕ compartments where these phospholipids are confined for 0.33 s on average. The diffusion rate within 230-nm compartments is 5.4 μm2/s, which is nearly as fast as that in large unilamellar vesicles, indicating that the diffusion in the cell membrane is reduced not because diffusion per se is slow, but because the cell membrane is compartmentalized with regard to lateral diffusion of phospholipids. Such compartmentalization depends on the actin-based membrane skeleton, but not on the extracellular matrix, extracellular domains of membrane proteins, or cholesterol-enriched rafts. We propose that various transmembrane proteins anchored to the actin-based membrane skeleton meshwork act as rows of pickets that temporarily confine phospholipids.
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10 June 2002
Article|
June 10 2002
Phospholipids undergo hop diffusion in compartmentalized cell membrane
In Special Collection:
JCB65: Lipid and Membrane Biology
Takahiro Fujiwara,
Takahiro Fujiwara
1Kusumi Membrane Organizer Project, Exploratory Research for Advanced Technology Organization (ERATO), Japan Science and Technology Corporation, Nagoya 460-0012, Japan
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Ken Ritchie,
Ken Ritchie
1Kusumi Membrane Organizer Project, Exploratory Research for Advanced Technology Organization (ERATO), Japan Science and Technology Corporation, Nagoya 460-0012, Japan
2Department of Biological Science, Nagoya University, Nagoya 464-8602, Japan
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Hideji Murakoshi,
Hideji Murakoshi
2Department of Biological Science, Nagoya University, Nagoya 464-8602, Japan
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Ken Jacobson,
Ken Jacobson
3Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
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Akihiro Kusumi
Akihiro Kusumi
1Kusumi Membrane Organizer Project, Exploratory Research for Advanced Technology Organization (ERATO), Japan Science and Technology Corporation, Nagoya 460-0012, Japan
2Department of Biological Science, Nagoya University, Nagoya 464-8602, Japan
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Takahiro Fujiwara
1Kusumi Membrane Organizer Project, Exploratory Research for Advanced Technology Organization (ERATO), Japan Science and Technology Corporation, Nagoya 460-0012, Japan
Ken Ritchie
1Kusumi Membrane Organizer Project, Exploratory Research for Advanced Technology Organization (ERATO), Japan Science and Technology Corporation, Nagoya 460-0012, Japan
2Department of Biological Science, Nagoya University, Nagoya 464-8602, Japan
Hideji Murakoshi
2Department of Biological Science, Nagoya University, Nagoya 464-8602, Japan
Ken Jacobson
3Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
Akihiro Kusumi
1Kusumi Membrane Organizer Project, Exploratory Research for Advanced Technology Organization (ERATO), Japan Science and Technology Corporation, Nagoya 460-0012, Japan
2Department of Biological Science, Nagoya University, Nagoya 464-8602, Japan
Address correspondence to Akihiro Kusumi, Department of Biological Science, Nagoya University, Nagoya 464-8602, Japan. Tel.: 81-52-789-2969. Fax: 81-52-789-2968. E-mail: [email protected]
The online version of this article includes supplemental material.
*
Abbreviations used in this paper: ϕ, diameter; DMACRO, macroscopic diffusion coefficient; Dmicro, microscopic diffusion coefficient; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; LUV, large unilamellar vesicle; MSD, mean square displacement; NRK, normal rat kidney fibroblastic cell; SPT, single particle tracking; TfR, transferrin receptor.
Received:
February 12 2002
Revision Received:
April 22 2002
Accepted:
April 23 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 157 (6): 1071–1082.
Article history
Received:
February 12 2002
Revision Received:
April 22 2002
Accepted:
April 23 2002
Citation
Takahiro Fujiwara, Ken Ritchie, Hideji Murakoshi, Ken Jacobson, Akihiro Kusumi; Phospholipids undergo hop diffusion in compartmentalized cell membrane . J Cell Biol 10 June 2002; 157 (6): 1071–1082. doi: https://doi.org/10.1083/jcb.200202050
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