title: Elasticity Modulation of Fibroblast-Derived Matrix for Endothelial Cell Vascular Morphogenesis and Mesenchymal Stem Cell Differentiation.
abstract: Biophysical properties of the microenvironment, including matrix elasticity and topography, are known to affect various cell behaviors; however, the specific role of each factor is unclear. In this study, fibroblast-derived matrix (FDM) was used as cell culture substrate and physically modified to investigate the influence of its biophysical property changes on human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) behavior in vitro. These FDMs were physically modified by simply storing them at different temperatures: the one stored at 4°C, maintained its original properties, was considered natural FDM, whereas the ones stored at -20°C or -80°C, exhibited a distinct surface morphology, were considered physically modified FDM. Physical modification induced matrix fiber rearrangement in FDM, forming different microstructures on the surface as characterized by focused ion beam (FIB)-cryoSEM. A significant increase of matrix elasticity was found with physically modified FDMs as determined by atomic force microscopy. HUVEC and hMSC behaviors on these natural and physically modified FDMs were observed and compared with each other and with gelatin-coated coverslips. HUVECs showed a similar adhesion level on these substrates at 3 h, but exhibited different proliferation rates and morphologies at 24 h; HUVECs on natural FDM proliferated relatively slower and assembled to capillary-like structures (CLSs). It is observed that HUVECs assembled to CLSs on natural FDMs are independent on the exogenous growth factors and yet dependent on nonmuscle myosin II activity. This result indicates the important role of matrix mechanical properties in regulating HUVECs vascular morphogenesis. As for hMSCs multilineage differentiation, adipogenesis is improved on natural FDM that with lower matrix elasticity, while osteogenesis is accelerated on physically modified FDMs that with higher matrix elasticity, these results further confirm the crucial role of matrix elasticity on cell fate determination.
authors.affiliation: 1 Center for Biomaterials, Korea Institute of Science and Technology , Seoul, Republic of Korea.|2 Department of Biomedical Engineering, Korea University of Science and Technology , Daejeon, Republic of Korea.
authors.forename: Ping
authors.initials: P
authors.lastname: Du
authors.affiliation: 1 Center for Biomaterials, Korea Institute of Science and Technology , Seoul, Republic of Korea.|2 Department of Biomedical Engineering, Korea University of Science and Technology , Daejeon, Republic of Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Suhaeri
authors.affiliation: 1 Center for Biomaterials, Korea Institute of Science and Technology , Seoul, Republic of Korea.|2 Department of Biomedical Engineering, Korea University of Science and Technology , Daejeon, Republic of Korea.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Subbiah
authors.affiliation: 1 Center for Biomaterials, Korea Institute of Science and Technology , Seoul, Republic of Korea.|2 Department of Biomedical Engineering, Korea University of Science and Technology , Daejeon, Republic of Korea.
authors.forename: Se Young
authors.initials: SY
authors.lastname: Van
authors.affiliation: 1 Center for Biomaterials, Korea Institute of Science and Technology , Seoul, Republic of Korea.
authors.forename: Jimin
authors.initials: J
authors.lastname: Park
authors.affiliation: 1 Center for Biomaterials, Korea Institute of Science and Technology , Seoul, Republic of Korea.|2 Department of Biomedical Engineering, Korea University of Science and Technology , Daejeon, Republic of Korea.
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: 1 Center for Biomaterials, Korea Institute of Science and Technology , Seoul, Republic of Korea.|2 Department of Biomedical Engineering, Korea University of Science and Technology , Daejeon, Republic of Korea.
authors.forename: Kwideok
authors.initials: K
authors.lastname: Park
authors.affiliation: 3 Program in Nanoscience and Technology, Graduate School of Convergence Science and Technology, Seoul National University , Seoul, Republic of Korea.|4 Advanced Institutes of Convergence Technology , Gyeonggi-do, Republic of Korea.
authors.forename: Kangwon
authors.initials: K
authors.lastname: Lee
mesh_terms: D050156:Adipogenesis; D000818:Animals; D055592:Biophysical Phenomena; D002196:Capillaries / Q000502:physiology; D002448:Cell Adhesion; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D048430:Cell Shape; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000648:ultrastructure; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009024:Morphogenesis; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D010012:Osteogenesis; D014945:Wound Healing
chemical_list: D024507:Nonmuscle Myosin Type IIA