title: Mechano-sensing and transduction by endothelial surface glycocalyx: composition, structure, and function.
abstract: The endothelial cells (ECs) lining every blood vessel wall are constantly exposed to the mechanical forces generated by blood flow. The EC responses to these hemodynamic forces play a critical role in the homeostasis of the circulatory system. To ensure proper EC mechano-sensing and transduction, there are a variety of mechano-sensors and transducers that have been identified on the EC surface, intra- and trans-EC membrane and within the EC cytoskeleton. Among them, the most recent candidate is the endothelial surface glycocalyx (ESG), which is a matrix-like thin layer covering the luminal surface of the EC. It consists of various proteoglycans, glycosaminoglycans, and plasma proteins, and is close to other prominent EC mechano-sensors and transducers. The ESG thickness was found to be in the order of 0.1-1 µm by different visualization techniques and in different types of vessels. Detailed analysis on the electron microscopy (EM) images of the microvascular ESG revealed a quasi-periodic substructure with the ESG fiber diameter of 10-12 and 20 nm spacing between adjacent fibers. Atomic force microscopy and optical tweezers were applied to investigate the mechanical properties of the ESG on the cultured EC monolayers and in solutions. Enzymatic degradation of specific ESG glycosaminoglycan components was used to directly elucidate the role of the ESG in EC mechano-sensing and transduction by measuring the shear-induced productions of nitric oxide and prostacyclin, two characteristic responses of the ECs to the flow. The unique location, composition, and structure of the ESG determine its role in EC mechano-sensing and transduction.
authors: Department of Biomedical Engineering, The City College of the City University of New York, New York, NY, USA. fu@ccny.cuny.edu
authors: Bingmei M
authors: BM
authors: Fu
authors: John M
authors: JM
authors: Tarbell
mesh_terms: D001794:Blood Pressure / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D019276:Glycocalyx / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D006025:Glycosaminoglycans / Q000737:chemistry; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry
chemical_list: D015815:Cell Adhesion Molecules; D006025:Glycosaminoglycans; D011509:Proteoglycans; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
references: Ann Med. 2003;35(8):564-77
references: 14708967
references: Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16483-8
references: 15545600
references: Nat Rev Mol Cell Biol. 2009 Jan;10(1):75-82
references: 19197334
references: Clin Hemorheol Microcirc. 2004;30(3-4):185-200
references: 15258343
references: J Clin Invest. 1984 Apr;73(4):1121-9
references: 6707208
references: J Appl Physiol (1985). 2012 Oct;113(7):1141-53
references: 22858626
references: Mol Biol Cell. 2011 Nov;22(22):4324-34
references: 21937718
references: J Vasc Res. 2007;44(2):87-98
references: 17192719
references: Am J Physiol Lung Cell Mol Physiol. 2011 Sep;301(3):L353-60
references: 21705487
references: Cell Mol Bioeng. 2011 Jun 1;4(2):169-181
references: 22247740
references: Dis Model Mech. 2008 Sep-Oct;1(2-3):175-81; discussion 179
references: 19048083
references: Curr Opin Cell Biol. 2008 Oct;20(5):551-6
references: 18583124
references: Sci Signal. 2008 Oct 07;1(40):pt8
references: 18840877
references: Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1908-15
references: 21474821
references: Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1023-30
references: 17468337
references: PLoS One. 2012;7(8):e43168
references: 22905223
references: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7988-95
references: 12810946
references: J Physiol. 1992 Jan;445:473-86
references: 1501143
references: Fed Proc. 1966 Nov-Dec;25(6):1773-83
references: 5927412
references: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10060-5
references: 15220478
references: Microvasc Res. 1997 Jan;53(1):1-13
references: 9056471
references: J Vasc Res. 2011;48(4):297-306
references: 21273784
references: Am J Physiol. 1991 Dec;261(6 Pt 2):H2016-23
references: 1721502
references: Circ Res. 2003 Apr 4;92(6):592-4
references: 12637366
references: Biophys J. 2011 Sep 7;101(5):1046-56
references: 21889441
references: Circ Res. 1996 Sep;79(3):581-9
references: 8781491
references: J Cell Sci. 2012 Jul 1;125(Pt 13):3061-73
references: 22797927
references: Circ Res. 2005 Mar 18;96(5):488-500
references: 15774861
references: J Pharmacol Sci. 2011;116(4):323-31
references: 21757846
references: Eur J Morphol. 1993 Dec;31(4):251-5
references: 8172755
references: Circ Res. 2003 Nov 14;93(10):e136-42
references: 14563712
references: Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1209-24
references: 17098825
references: Interface Focus. 2011 Oct 6;1(5):754-66
references: 23050080
references: Biochem Biophys Res Commun. 2007 Mar 30;355(1):228-33
references: 17291452
references: Microcirculation. 2012 May;19(4):343-51
references: 22324320
references: J Biol Chem. 2006 Dec 1;281(48):36492-500
references: 16973617
references: Am J Physiol Renal Physiol. 2001 Mar;280(3):F396-405
references: 11181401
references: Pflugers Arch. 2000 Sep;440(5):653-66
references: 11007304
references: J Appl Physiol (1985). 2005 Jun;98(6):2355-62
references: 15705727
references: Pflugers Arch. 2009 Apr;457(6):1199-206
references: 18839207
references: Microvasc Res. 2004 Sep;68(2):110-8
references: 15313120
references: Microvasc Res. 2012 May;83(3):337-46
references: 22349291
references: Kidney Int. 2011 Jun;79(12):1322-30
references: 21412215
references: Cold Spring Harb Perspect Biol. 2011 Jul 01;3(7):
references: 21690215
references: Biorheology. 2001;38(2-3):143-50
references: 11381171
references: J Histochem Cytochem. 1984 Mar;32(3):259-66
references: 6198357
references: Biophys J. 2003 Jul;85(1):637-45
references: 12829517
references: Exp Cell Res. 2004 Apr 15;295(1):102-18
references: 15051494
references: Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H722-6
references: 12730059
references: Annu Rev Biomed Eng. 2007;9:121-67
references: 17373886
references: J Physiol. 1988 Jan;395:99-114
references: 3261792
references: Phys Biol. 2009 Jul 01;6(2):025014
references: 19571362
references: J Intern Med. 2006 Apr;259(4):339-50
references: 16594902
references: J R Soc Interface. 2012 Sep 7;9(74):2290-8
references: 22417911
references: Am J Physiol. 1993 Sep;265(3 Pt 2):H828-33
references: 8105699
references: J Clin Invest. 1997 Dec 1;100(11 Suppl):S67-75
references: 9413405
references: Science. 1985 Mar 22;227(4693):1477-9
references: 3883488
references: Physiol Rev. 1995 Jul;75(3):519-60
references: 7624393
references: J Struct Biol. 2001 Dec;136(3):239-55
references: 12051903
references: Am J Physiol Renal Physiol. 2001 Apr;280(4):F646-56
references: 11249856
references: Differentiation. 2012 Feb;83(2):S56-61
references: 22169885
references: Microvasc Res. 2010 Dec;80(3):394-401
references: 20600162