Mechanistic insights into the adsorption and bioactivity of fibronectin on surfaces with varying chemistries by a combination of experimental strategies and molecular simulations  

作　　者：Lijing Hao Tianjie Li Lin Wang Xuetao Shi Yan Fan Chang Du Yingjun Wang 

机构地区：[1]School of Materials Science and Engineering,South China University of Technology,Guangzhou,510640,China [2]Department of Physics,The Chinese University of Hong Kong,Shatin,N.T.,Hong Kong [3]National Engineering Research Center for Tissue Restoration and Reconstruction,Guangzhou,510006,China [4]Key Laboratory of Biomedical Engineering of Guangdong Province,Guangzhou,510006,China [5]Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education,Guangzhou,510006,China [6]Innovation Center for Tissue Restoration and Reconstruction,Guangzhou,510006,China [7]Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou,510005,China

出　　处：《Bioactive Materials》2021年第10期3125-3135,共11页生物活性材料（英文）

基　　金：This work was financially supported by National key R&D Program of China(2018YFC1105402,2017YFC1104402,2017YFC1105000);National Natural Science Foundation of China(31700823,U1801252,31771027);Natural Science Foundation of Guangdong Province of China(2020A1515011354,2017A030310335);Science and Technology Program of Guangzhou(201804020060);the Guangdong Natural Science Funds for Distinguished Young Scholars(2019B151502029);the Pearl River Nova Program of Guangzhou(201806010156);Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110102001);the Fundamental Research Funds for the Central Universities;L.W.thanks the Funds for Young Pearl River Scholars.

摘　　要：Fibronectin(Fn)is significant to the performance of biomaterials,and the chemistry of biomaterial surface play important roles in Fn adsorption and subsequent cell behavior.However,the“molecular scale”mechanism is still unclear.Herein,we combined experimental strategies with molecular simulations to solve this problem.We prepared self-assembled monolayers with varying chemistries,i.e.,SAMs-CH3,SAMs-NH2,SAMs-COOH and SAMs-OH,and characterized Fn adsorption and cell behaviors on them.Next,Monte Carlo method and all-atom molecular dynamics simulations were employed to reveal the orientation/conformation of Fn on surfaces.We found that SAMs-CH3 strongly adsorbed Fn via hydrophobic interactions,but show poor bioactivity as the low exposure of RGD/PHSRN motifs and the deformation of Fn.SAMs-NH2 and SAMs-COOH could adsorb Fn efficiently via vdW interactions,electrostatic interactions,hydrogen bonds and salt bridges.Fn exhibited excellent bioactivity for cell adhesion,proliferation and osteogenic differentiation as high exposure of bioactive motifs on SAMs-NH2,or as the activation of other inferior cell-binding motifs on SAMs-COOH.SAMs-OH showed poor Fn adsorption as the water film.However,the adsorbed Fn displayed non-negligible bioactivity due to high exposure of PHSRN motif and large degree of protein flexibility.We believe that the revealed mechanism presents great potential to rationally design Fn-activating biomaterials.

关 键 词：FIBRONECTIN SELF-ASSEMBLED HBMSCS Molecular dynamics simulation Orientation 

分 类 号：R318[医药卫生—生物医学工程]