In micropipette aspiration experiment,increasing mechanical stress applied to cell membrane induced degranulation of mast cell as well as a current that could be inhibited by an inhibitor, which is specific for the tr...In micropipette aspiration experiment,increasing mechanical stress applied to cell membrane induced degranulation of mast cell as well as a current that could be inhibited by an inhibitor, which is specific for the transient receptor potential vanilloid(TRPVs) channels. To determine the sensitivity of TRPVs to membrane strain and tension, and to gain new insights into the activation mechanism of TRPVs, finite element models of mast cell and molecular dynamic simulations of human aquaporin-1are presented. During the finite element simulations, the cell membrane sustained to micropipette aspiration was simulated, and the strain distribution along membrane thickness direction was obtained. Besides, combining the finite element models of osteoblast aspirated into micropipette and other compared models, we examined the relationship between cell mechanical attributes and mechanical stimulations and presented a new perspective to determine the cell equivalent elastic modulus. Considering the indetermination of TRPV crystal structure, human aquaporin-1, one kind of the channel membrane proteins,substituting for TRPV, has been studied with molecular dynamic(MD) simulations, under different external lateral tensions which have been obtained in mast cell finite element simulations, to investigate the mechanical stimulation effects on the membrane channels. The simulations show that human aquaporin-1 undergoes significant conformational change and expands in accordance with lateral tension, which not only confirms the tendency of the previous electrophysiological experiments but also leads us to a better understanding of TRPVs. The multi-scale study combining finite element simulation and MD simulation is a significant breakthrough in the field of mechanical mechanism in cell system.展开更多
基金supported by the National Basic Research Program of China(2012CB518502)the National Natural Science Foundation of China(81102630)+2 种基金the Shanghai Leading Academic Discipline Project(S30304,B112)the Science Foundationof Shanghai Municipal Commission of Science and Technology(09DZ1976600,09dZ1974303,10DZ1975800)Fudan Young Teacher’s Research Foundation(09FQ07)
文摘In micropipette aspiration experiment,increasing mechanical stress applied to cell membrane induced degranulation of mast cell as well as a current that could be inhibited by an inhibitor, which is specific for the transient receptor potential vanilloid(TRPVs) channels. To determine the sensitivity of TRPVs to membrane strain and tension, and to gain new insights into the activation mechanism of TRPVs, finite element models of mast cell and molecular dynamic simulations of human aquaporin-1are presented. During the finite element simulations, the cell membrane sustained to micropipette aspiration was simulated, and the strain distribution along membrane thickness direction was obtained. Besides, combining the finite element models of osteoblast aspirated into micropipette and other compared models, we examined the relationship between cell mechanical attributes and mechanical stimulations and presented a new perspective to determine the cell equivalent elastic modulus. Considering the indetermination of TRPV crystal structure, human aquaporin-1, one kind of the channel membrane proteins,substituting for TRPV, has been studied with molecular dynamic(MD) simulations, under different external lateral tensions which have been obtained in mast cell finite element simulations, to investigate the mechanical stimulation effects on the membrane channels. The simulations show that human aquaporin-1 undergoes significant conformational change and expands in accordance with lateral tension, which not only confirms the tendency of the previous electrophysiological experiments but also leads us to a better understanding of TRPVs. The multi-scale study combining finite element simulation and MD simulation is a significant breakthrough in the field of mechanical mechanism in cell system.
