Receptor-ligand interactions in blood flow are crucial to initiate such biological processes as inflammatory cascade,platelet thrombosis,as well as tumor metastasis.To mediate cell adhesion,the interacting receptors a...Receptor-ligand interactions in blood flow are crucial to initiate such biological processes as inflammatory cascade,platelet thrombosis,as well as tumor metastasis.To mediate cell adhesion,the interacting receptors and ligands must be anchored onto two apposing surfaces of two cells or a cell and a substratum,i.e.,two-dimensional（2D）binding,which is different from the binding of a soluble ligand in fluid phase to a receptor,i.e.,three-dimensional（3D） binding.While numerous works have been focused on3 D kinetics of receptor-ligand interactions in the immune system,2D kinetics and its regulations have been less understood,since no theoretical framework or experimental assays were established until 1993.Not only does the molecular structure dominate 2D binding kinetics,but the shear force in blood flow also regulates cell adhesion mediated by interacting receptors and ligands.Here,we provide an overview of current progress in 2D binding and regulations,mainly from our group.Relevant issues of theoretical frameworks,experimental measurements,kinetic rates and binding affinities,and force regulations are discussed.展开更多
We present an extended analytical model including the depletion effect and the dimension of ligand-receptor complex, aiming to elucidate their influences on endocytosis of spherocylindrical nanoparticles （NPs）. It i...We present an extended analytical model including the depletion effect and the dimension of ligand-receptor complex, aiming to elucidate their influences on endocytosis of spherocylindrical nanoparticles （NPs）. It is found that the dimension of ligand-receptor complex （δ） and the depletion effect interrelatedly govern the optimal conditions of NP endocytosis. The endocytosis phase diagram constructed in the space of NP radius and relative aspect ratio indicates that the endocytosis of NP is enhanced evidently by reducing the optimal radius and the threshold radius of endocytosed NP. Meanwhile, through thermodynamic and kinetic analysis of the diffusion of receptors, the dependence of diffusion length on depletion effect and the dimension of ligand-receptor complex can be identified in great detail. For small aspect ratio, diffusion length decreases with increasing concentration c of small bioparticles in cellular environment. Endocytosis speed corresponding to large radius R and high concentration c of small bioparticles strongly depends on the increasing （2r-δ）. These results may show some highlights into the conscious design of NPs for diagnostic agents and therapeutic drug delivery applications.展开更多
地舒单抗(denosumab,DMAb)是最早出现的全人源核因子-κB受体活化因子配体[receptor activator of nuclear factor-κB(NF-κB)ligand,RANKL]的单克隆抗体。2020年在我国上市,应用于骨质疏松治疗领域,是抑制骨吸收类抗骨松药物中的新成...地舒单抗(denosumab,DMAb)是最早出现的全人源核因子-κB受体活化因子配体[receptor activator of nuclear factor-κB(NF-κB)ligand,RANKL]的单克隆抗体。2020年在我国上市,应用于骨质疏松治疗领域,是抑制骨吸收类抗骨松药物中的新成员。本综述的目的为归纳总结近年围绕DMAb在骨质疏松初始、序贯以及联合治疗方面的临床研究进展,为其应用提供参考。展开更多
基金supported by Natural Science Foundation of China(grants 10042001,10072071,10128205,30225027, 10332060,30730032,11072251,and 31110103918)National Key Basic Research Foundation of China(grants 2006CB910303 and 2011CB710904)+2 种基金National High Technology Research and Development Program of China(grants 2007AA02Z306 and 2011AA020109)Chinese Academy of Sciences(grants KJCX2-L02,KJCX2-SW-L06, 2005-1-16,KJCX2-YW-L08,Y2010030,XDA01030102,XDA04073 801)NIH Fogarty International Research Collaboration Award TW 05774-01
文摘Receptor-ligand interactions in blood flow are crucial to initiate such biological processes as inflammatory cascade,platelet thrombosis,as well as tumor metastasis.To mediate cell adhesion,the interacting receptors and ligands must be anchored onto two apposing surfaces of two cells or a cell and a substratum,i.e.,two-dimensional（2D）binding,which is different from the binding of a soluble ligand in fluid phase to a receptor,i.e.,three-dimensional（3D） binding.While numerous works have been focused on3 D kinetics of receptor-ligand interactions in the immune system,2D kinetics and its regulations have been less understood,since no theoretical framework or experimental assays were established until 1993.Not only does the molecular structure dominate 2D binding kinetics,but the shear force in blood flow also regulates cell adhesion mediated by interacting receptors and ligands.Here,we provide an overview of current progress in 2D binding and regulations,mainly from our group.Relevant issues of theoretical frameworks,experimental measurements,kinetic rates and binding affinities,and force regulations are discussed.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11047022,11204045,and 11464004)the Tracking Key Program of Social Development of Guizhou Province,China(Grant Nos.SY20123089 and SZ20113069)+2 种基金the General Financial Grant from the China Postdoctoral Science Foundation(Grant No.2014M562341)the Research Foundation for Young University Teachers from Guizhou University(Grant No.201311)the College Innovation Talent Team of Guizhou Province,China(Grant No.(2014)32)
文摘We present an extended analytical model including the depletion effect and the dimension of ligand-receptor complex, aiming to elucidate their influences on endocytosis of spherocylindrical nanoparticles （NPs）. It is found that the dimension of ligand-receptor complex （δ） and the depletion effect interrelatedly govern the optimal conditions of NP endocytosis. The endocytosis phase diagram constructed in the space of NP radius and relative aspect ratio indicates that the endocytosis of NP is enhanced evidently by reducing the optimal radius and the threshold radius of endocytosed NP. Meanwhile, through thermodynamic and kinetic analysis of the diffusion of receptors, the dependence of diffusion length on depletion effect and the dimension of ligand-receptor complex can be identified in great detail. For small aspect ratio, diffusion length decreases with increasing concentration c of small bioparticles in cellular environment. Endocytosis speed corresponding to large radius R and high concentration c of small bioparticles strongly depends on the increasing （2r-δ）. These results may show some highlights into the conscious design of NPs for diagnostic agents and therapeutic drug delivery applications.
文摘地舒单抗(denosumab,DMAb)是最早出现的全人源核因子-κB受体活化因子配体[receptor activator of nuclear factor-κB(NF-κB)ligand,RANKL]的单克隆抗体。2020年在我国上市,应用于骨质疏松治疗领域,是抑制骨吸收类抗骨松药物中的新成员。本综述的目的为归纳总结近年围绕DMAb在骨质疏松初始、序贯以及联合治疗方面的临床研究进展,为其应用提供参考。
