Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the ma...Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the major sites of interaction between a cell and its extracellular matrix（ECM）microenvironment,thus outside mechanical signals can be sensed at focal adhesions through transmembrane receptor integrins.In particular,it has been shown that matrix elasticity can control the cell fate<sup>[4]</sup>by modulating the interactions between ECM proteins and their receptor integrins<sup>[5,6]</sup>.For example,different rigidity of polyacrylamide（PA）gels can lead to different density of ECM ancho-展开更多
We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin(α2A),providing valuable new insights into the mechanisms and ...We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin(α2A),providing valuable new insights into the mechanisms and dynamics of collagen-integrin binding at a sub-molecular level.The occurrence of single and triple-helical strands of the collagen fragments was scrutinized with atom force microscopy(AFM)techniques.Strong interactions of the triple-stranded fragments comparable to those of collagen can only be detected for the 42mer triple-helical collagen-like peptide under study(which contains 42 amino acid residues per strand)by solid phase assays as well as by surface plasmon resonance(SPR)measurements.However,changes in NMR signals during titration and characteristic saturation transfer difference(STD)NMR signals are also detectable whenα2A is added to a solution of the 21mer single-stranded collagen fragment.Molecular dynamics(MD)simulations employing different sets of force field parameters were applied to study the interaction between triple-helical or single-stranded collagen fragments withα2A.It is remarkable that even single-stranded collagen fragments can form various complexes withα2A showing significant differences in the complex stability with identical ligands.The results of MD simulations are in agreement with the signal alterations in our NMR experiments,which are indicative of the formation of weak complexes between single-stranded collagen andα2A in solution.These results provide useful information concerning possible interactions ofα2A with small collagen fragments that are of relevance to the design of novel therapeutic A-domain inhibitors.展开更多
基金supported in part by NIH HL098472NSF CBET0846429
文摘Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the major sites of interaction between a cell and its extracellular matrix（ECM）microenvironment,thus outside mechanical signals can be sensed at focal adhesions through transmembrane receptor integrins.In particular,it has been shown that matrix elasticity can control the cell fate<sup>[4]</sup>by modulating the interactions between ECM proteins and their receptor integrins<sup>[5,6]</sup>.For example,different rigidity of polyacrylamide（PA）gels can lead to different density of ECM ancho-
文摘We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin(α2A),providing valuable new insights into the mechanisms and dynamics of collagen-integrin binding at a sub-molecular level.The occurrence of single and triple-helical strands of the collagen fragments was scrutinized with atom force microscopy(AFM)techniques.Strong interactions of the triple-stranded fragments comparable to those of collagen can only be detected for the 42mer triple-helical collagen-like peptide under study(which contains 42 amino acid residues per strand)by solid phase assays as well as by surface plasmon resonance(SPR)measurements.However,changes in NMR signals during titration and characteristic saturation transfer difference(STD)NMR signals are also detectable whenα2A is added to a solution of the 21mer single-stranded collagen fragment.Molecular dynamics(MD)simulations employing different sets of force field parameters were applied to study the interaction between triple-helical or single-stranded collagen fragments withα2A.It is remarkable that even single-stranded collagen fragments can form various complexes withα2A showing significant differences in the complex stability with identical ligands.The results of MD simulations are in agreement with the signal alterations in our NMR experiments,which are indicative of the formation of weak complexes between single-stranded collagen andα2A in solution.These results provide useful information concerning possible interactions ofα2A with small collagen fragments that are of relevance to the design of novel therapeutic A-domain inhibitors.
