title: Quantifying adhesion mechanisms and dynamics of human hematopoietic stem and progenitor cells.
abstract: Using planar lipid membranes with precisely defined concentrations of specific ligands, we have determined the binding strength between human hematopoietic stem cells (HSC) and the bone marrow niche. The relative significance of HSC adhesion to the surrogate niche models via SDF1α-CXCR4 or N-cadherin axes was quantified by (a) the fraction of adherent cells, (b) the area of tight adhesion, and (c) the critical pressure for cell detachment. We have demonstrated that the binding of HSC to the niche model is a cooperative process, and the adhesion mediated by the CXCR4- SDF1α axis is stronger than that by homophilic N-cadherin binding. The statistical image analysis of stochastic morphological dynamics unraveled that HSC dissipated energy by undergoing oscillatory deformation. The combination of an in vitro niche model and novel physical tools has enabled us to quantitatively determine the relative significance of binding mechanisms between normal HSC versus leukemia blasts to the bone marrow niche.
authors.affiliation: 1] Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany [2] Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany.
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Burk
authors.affiliation: Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Monzel
authors.affiliation: 1] Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany [2] Department of Chemistry, Faculty of Science, Saitama University, Saitama, 338-8570, Japan.
authors.forename: Hiroshi Y
authors.initials: HY
authors.lastname: Yoshikawa
authors.affiliation: Department of Medicine V (Hematology, Oncology &Rheumatology), University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wuchter
authors.affiliation: Department of Medicine V (Hematology, Oncology &Rheumatology), University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.affiliation: Department of Medicine V (Hematology, Oncology &Rheumatology), University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.affiliation: 1] Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany [2] Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany [3] Institute for Integrated Cell-Material Sciences (WPI iCeMS), Kyoto University, 606-8501, Kyoto, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Medicine V (Hematology, Oncology &Rheumatology), University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: D015820:Cadherins; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
references.citation: J Am Chem Soc. 2011 Feb 9;133(5):1367-74
references.pmid: 21218794
references.citation: Blood. 2012 Jul 12;120(2):295-302
references.pmid: 22323481
references.citation: Proc Natl Acad Sci U S A. 1989 Feb;86(4):1254-8
references.pmid: 2919174
references.citation: Biophys J. 2004 Oct;87(4):2855-69
references.pmid: 15454476
references.citation: Biophys J. 2006 Aug 1;91(3):1108-15
references.pmid: 16617074
references.citation: Exp Hematol. 1999 Dec;27(12):1806-14
references.pmid: 10641598
references.citation: Science. 1996 Jan 5;271(5245):43-8
references.pmid: 8539599
references.citation: Nat Biotechnol. 2007 Nov;25(11):1315-21
references.pmid: 17952057
references.citation: J Leukoc Biol. 2002 Mar;71(3):425-32
references.pmid: 11867680
references.citation: Blood. 1983 Jul;62(1):1-13
references.pmid: 6407542
references.citation: Blood. 2009 Aug 6;114(6):1150-7
references.pmid: 19401558
references.citation: Nature. 2003 Oct 23;425(6960):841-6
references.pmid: 14574413
references.citation: Cytotherapy. 2002;4(2):109-18
references.pmid: 12006206
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15320-5
references.pmid: 19717437
references.citation: Nature. 2010 Aug 12;466(7308):829-34
references.pmid: 20703299
references.citation: PLoS One. 2013;8(2):e54749
references.pmid: 23424619
references.citation: Exp Hematol. 2007 Feb;35(2):314-25
references.pmid: 17258080
references.citation: Nature. 2005 Sep 29;437(7059):656-63
references.pmid: 16193040
references.citation: Stem Cell Res. 2010 Mar;4(2):129-39
references.pmid: 20116358
references.citation: Nature. 1977 Sep 29;269(5627):412-4
references.pmid: 561894
references.citation: Chemphyschem. 2009 Nov 9;10(16):2828-38
references.pmid: 19821476
references.citation: Nature. 2003 Oct 23;425(6960):836-41
references.pmid: 14574412
references.citation: Nature. 1994 Mar 10;368(6467):113-9
references.pmid: 8139653
references.citation: PLoS One. 2012;7(8):e42991
references.pmid: 22916191
references.citation: Biophys J. 2005 Mar;88(3):1859-74
references.pmid: 15613626
references.citation: Nat Immunol. 2002 Jul;3(7):687-94
references.pmid: 12068293
references.citation: Blood. 1998 Jun 15;91(12):4523-30
references.pmid: 9616148
references.citation: J Clin Invest. 1999 Nov;104(9):1199-211
references.pmid: 10545519
references.citation: J Chem Phys. 2012 Nov 28;137(20):204907
references.pmid: 23206031
references.citation: Cytotherapy. 2014 Jan;16(1):111-21
references.pmid: 24119647
references.citation: Biomaterials. 1998 Apr-May;19(7-9):871-9
references.pmid: 9663764
references.citation: J Physiol. 1910 Mar 8;39(6):411-28
references.pmid: 16992995
references.citation: J Cell Sci. 1987 May;87 ( Pt 4):519-23
references.pmid: 3654789
references.citation: Nature. 1999 Jan 7;397(6714):50-3
references.pmid: 9892352
references.citation: Cell Stem Cell. 2009 Feb 6;4(2):170-9
references.pmid: 19119091
references.citation: J Clin Invest. 2003 Jan;111(2):187-96
references.pmid: 12531874
references.citation: Endocr Rev. 2000 Feb;21(1):90-113
references.pmid: 10696571
references.citation: N Engl J Med. 1999 Sep 30;341(14):1051-62
references.pmid: 10502596
references.citation: J Phys Chem B. 2013 May 2;117(17):5002-8
references.pmid: 23586470
references.citation: J Biomed Biotechnol. 2007;2007(3):26065
references.pmid: 17541466
references.citation: Cell Stem Cell. 2010 Mar 5;6(3):199-202
references.pmid: 20207222
references.citation: Nat Med. 1997 Jul;3(7):730-7
references.pmid: 9212098
references.citation: Blood. 2012 Jul 12;120(2):303-13
references.pmid: 22596259
references.citation: Bone Marrow Transplant. 1989 Nov;4(6):643-6
references.pmid: 2573397
references.citation: J Clin Invest. 2000 Dec;106(11):1331-9
references.pmid: 11104786
references.citation: Cell Stem Cell. 2010 Mar 5;6(3):194-8
references.pmid: 20207221
references.citation: Exp Hematol. 2003 Apr;31(4):339-47
references.pmid: 12691922
references.citation: J Cell Sci. 2001 Apr;114(Pt 8):1567-77
references.pmid: 11282032
references.citation: Biophys J. 1999 Jan;76(1 Pt 1):573-9
references.pmid: 9876170
references.citation: J Exp Med. 1997 Jan 6;185(1):111-20
references.pmid: 8996247
references.citation: J Cell Mol Med. 2010 Jan;14(1-2):337-50
references.pmid: 19432817
references.citation: PLoS One. 2008;3(11):e3734
references.pmid: 19011688
references.citation: Lancet. 1993 Jun 5;341(8858):1482
references.pmid: 8099182
references.citation: Curr Opin Cell Biol. 2011 Oct;23(5):523-30
references.pmid: 21890337