Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Sep 1981; 78(9): 5695–5698.
PMCID: PMC348831

Interactions of low density lipoprotein receptors with coated pits on human fibroblasts: estimate of the forward rate constant and comparison with the diffusion limit.


We present a theoretical study of the interaction of low density lipoprotein (LDL) receptors with coated pits. From published experiments we estimate that the forward rate constant, k+, for the binding of a LDL receptor to a coated pit on a human fibroblast at 37 degrees C is greater than or equal to 3 X 10(-10) cm2/sec, and the mean time an LDL receptor spends on the cell surface before being captured by a coated pit, tc, is less than or equal to 1.8 min. If, when an LDL receptor enters, it remains within the coated pit until the coated pit pinches off to form a coated vesicle, then k+ = 3 X 10(-10) cm2/sec and tc = 1.8 min. We derive expressions for the diffusion limit of k+ and tc when particles (LDL receptors) diffuse in two dimensions until they hit and are absorbed by circular absorbers (coated pits) that have finite lifetimes. The absorbers appear and disappear at equal rates so that their concentration remains constant. We use these expressions to show that a diffusion limit of k+ = 3 X 10(-10) cm2/ sec would be obtained if D, the diffusion coefficient for an LDL receptor on a human fibroblast at 37 degrees C equaled 3.3 X 10(-11) cm2/sec. Because this value is in agreement with the experimentally determined value for D, we conclude that random insertion of LDL receptors into the plasma membrane, followed by pure diffusional motion of LDL receptors on the cell surface until they are irreversibly absorbed in coated pits, is consistent with experiment.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (847K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Goldstein JL, Brown MS. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Aug 25;249(16):5153–5162. [PubMed]
  • Brown MS, Goldstein JL. Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Cell. 1975 Nov;6(3):307–316. [PubMed]
  • Anderson RG, Goldstein JL, Brown MS. Localization of low density lipoprotein receptors on plasma membrane of normal human fibroblasts and their absence in cells from a familial hypercholesterolemia homozygote. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2434–2438. [PMC free article] [PubMed]
  • Goldstein JL, Basu SK, Brunschede GY, Brown MS. Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans. Cell. 1976 Jan;7(1):85–95. [PubMed]
  • Anderson RG, Goldstein JL, Brown MS. A mutation that impairs the ability of lipoprotein receptors to localise in coated pits on the cell surface of human fibroblasts. Nature. 1977 Dec 22;270(5639):695–699. [PubMed]
  • Anderson RG, Brown MS, Goldstein JL. Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts. Cell. 1977 Mar;10(3):351–364. [PubMed]
  • Brown MS, Goldstein JL. Receptor-mediated endocytosis: insights from the lipoprotein receptor system. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3330–3337. [PMC free article] [PubMed]
  • Goldstein JL, Anderson RG, Brown MS. Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature. 1979 Jun 21;279(5715):679–685. [PubMed]
  • Brown MS, Goldstein JL. Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein. Cell. 1976 Dec;9(4 Pt 2):663–674. [PubMed]
  • Orci L, Carpentier JL, Perrelet A, Anderson RG, Goldstein JL, Brown MS. Occurrence of low density lipoprotein receptors within large pits on the surface of human fibroblasts as demonstrated by freeze-etching. Exp Cell Res. 1978 Apr;113(1):1–13. [PubMed]
  • Carpentier JL, Gorden P, Goldstein JL, Anderson RG, Brown MS, Orci L. Binding and internalization of 125I-LDL in normal and mutant human fibroblasts. A quantitative autoradiographic study. Exp Cell Res. 1979 Jun;121(1):135–142. [PubMed]
  • Vermeer BJ, Havekes L, Wijsman MC, Emeis JJ. Immunoelectronmicroscopical investigations on the adsorptive endocytosis of low density lipoproteins by human fibroblasts. Exp Cell Res. 1980 Sep;129(1):201–210. [PubMed]
  • Anderson RG, Vasile E, Mello RJ, Brown MS, Goldstein JL. Immunocytochemical visualization of coated pits and vesicles in human fibroblasts: relation to low density lipoprotein receptor distribution. Cell. 1978 Nov;15(3):919–933. [PubMed]
  • Heuser J. Three-dimensional visualization of coated vesicle formation in fibroblasts. J Cell Biol. 1980 Mar;84(3):560–583. [PMC free article] [PubMed]
  • Berg HC, Purcell EM. Physics of chemoreception. Biophys J. 1977 Nov;20(2):193–219. [PMC free article] [PubMed]
  • DeLisi C. The biophysics of ligand-receptor interactions. Q Rev Biophys. 1980 May;13(2):201–230. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...