title: Migration mechanism of mesenchymal stem cells studied by QD/NSOM.
abstract: The migration of mesenchymal stem cells (MSCs) plays a key role in tumor-targeted delivery vehicles and tumor-related stroma formation. However, there so far has been no report on the distribution of cell surface molecules during the VEGF-induced migration of MSCs. Here, we have utilized near-field scanning optical microscopy (NSOM) combined with fluorescent quantum dot (QD)-based nano-technology to capture the functional relationship between CD44 and CD29 adhesion molecules on MSCs and the effect of their spatial rearrangements. Before VEGF-induced migration of MSCs, both CD44 and CD29 formed 200-220 nm nano-domains respectively, with little co-localization between the two types of domains. Surprisingly, the size of the CD44 nano-domain rapidly increased in size to 295 nm and apparently larger aggregates were formed following MSC treatment with VEGF for 10 min, while the area of co-localization increased to 0.327 μm2. Compared with CD44, CD29 was activated obviously later, for the fact that CD29 aggregation didn't appear until 30 min after VEGF treatment. Consistently, its co-localization area increased to 0.917 μm2. The CD44 and CD29 nano-domains further aggregated into larger nano-domains or even formed micro-domains on the membrane of activated MSCs. The aggregation and co-localization of these molecules promoted FAK formation and cytoskeleton rearrangement. All of the above changes induced by VEGF contributed to MSC migration. Taken together, our data of NSOM-based dual color fluorescent imaging demonstrated for the first time that CD44, together with CD29, involved in VEGF-induced migration of MSCs through the interaction between CD44 and its co-receptor of VEGFR-2.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Ke
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Jianan
authors.initials: J
authors.lastname: Chen
authors.affiliation: International Joint Cancer Institute and E-institutes of Shanghai Universities Immunology Division, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL 60612, USA.
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Cai
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005453:Fluorescence; D022001:Focal Adhesions / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D020527:Microscopy, Scanning Probe / Q000379:methods*; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D045663:Quantum Dots; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D019012:Integrin beta1; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: CD29; CD44; Mesenchymal stem cell; NSOM; QD; VEGF