Mechanosensation is an important process in biological fluid-structure interaction. To understand the biophysics underlying mechanosensation, it is essential to quantify the correlation between membrane deformation, m...Mechanosensation is an important process in biological fluid-structure interaction. To understand the biophysics underlying mechanosensation, it is essential to quantify the correlation between membrane deformation, membrane tension, external fluid shear stress, and conformation of mechanosensitive (MS) channels. Smoothed dissipative particle dynamics (SDPD) simulations of vesicle/cell in three types of flow configurations are conducted to calculate the tension in lipid membrane due to fluid shear stress from the surrounding viscous flow. In combination with a simple continuum model for an MS channel, SDPD simulation results suggest that shearing adhered vesicles/cells is more effective to induce membrane tension sufficient to stretch MS channels open than a free shear flow or a constrictive channel flow. In addition, we incorporate the bilayer-cytoskeletal interaction in a two-component model to probe the effects of a cytoskeletal network on the gating of MS channels.展开更多
Point-of-care molecular diagnostic tests show great promise for providing accurate,timely results in lowinfrastructure healthcare settings and at home.The design space for these tests is limited by a variety of possib...Point-of-care molecular diagnostic tests show great promise for providing accurate,timely results in lowinfrastructure healthcare settings and at home.The design space for these tests is limited by a variety of possible background reactions,which often originate from relatively weak promiscuous activities of the enzymes used for nucleic acid amplification.When this background signal is amplified alongside the signal of the intended biomarker,the dynamic range of the test can be severely compromised.Therefore,a detailed knowledge of potential side reactions arising from enzyme promiscuity can improve rational design of point-of-care molecular diagnostic tests.Towards this end,we report a previously unknown synergistic reaction between T7 RNA polymerase and Bsu DNA polymerase that produces nucleic acid in the presence of single-stranded DNA or RNA.This reaction occurs in the absence of any previously reported substrates for either polymerases and compromises a theoretical microRNA amplification scheme utilizing these polymerases.展开更多
文摘Mechanosensation is an important process in biological fluid-structure interaction. To understand the biophysics underlying mechanosensation, it is essential to quantify the correlation between membrane deformation, membrane tension, external fluid shear stress, and conformation of mechanosensitive (MS) channels. Smoothed dissipative particle dynamics (SDPD) simulations of vesicle/cell in three types of flow configurations are conducted to calculate the tension in lipid membrane due to fluid shear stress from the surrounding viscous flow. In combination with a simple continuum model for an MS channel, SDPD simulation results suggest that shearing adhered vesicles/cells is more effective to induce membrane tension sufficient to stretch MS channels open than a free shear flow or a constrictive channel flow. In addition, we incorporate the bilayer-cytoskeletal interaction in a two-component model to probe the effects of a cytoskeletal network on the gating of MS channels.
基金This work is supported by a generous gift from Kendall and Susan Warren and the NIH Director's New Innovator Award DP2 HL117748-01 to A.P.L.The authors wish to thank Maxwell DeNies,Lili Tian,and Jennifer Knister for helpful discussion.
文摘Point-of-care molecular diagnostic tests show great promise for providing accurate,timely results in lowinfrastructure healthcare settings and at home.The design space for these tests is limited by a variety of possible background reactions,which often originate from relatively weak promiscuous activities of the enzymes used for nucleic acid amplification.When this background signal is amplified alongside the signal of the intended biomarker,the dynamic range of the test can be severely compromised.Therefore,a detailed knowledge of potential side reactions arising from enzyme promiscuity can improve rational design of point-of-care molecular diagnostic tests.Towards this end,we report a previously unknown synergistic reaction between T7 RNA polymerase and Bsu DNA polymerase that produces nucleic acid in the presence of single-stranded DNA or RNA.This reaction occurs in the absence of any previously reported substrates for either polymerases and compromises a theoretical microRNA amplification scheme utilizing these polymerases.
