Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic fac...Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alternative understanding about the role of Al-GPlbαinteractions in the mechanism of hemostasis.展开更多
基金supported by the National Science Foundation of China ( 11772133, 11372116)the Fundamental Research Funds for the Central Universities ( HUST 0118012051)
文摘Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alternative understanding about the role of Al-GPlbαinteractions in the mechanism of hemostasis.
文摘青藏高原是全球重要的生态系统,其森林覆盖状况对全球气候变化和生态系统保护具有重要意义。为获取更为精确的青藏高原森林覆盖信息,本研究基于Sentinel-1、Sentinel-2遥感数据和DEM(Digital Elevation Model)数据,采用优化随机森林模型,生成了2021年青藏高原10米分辨率森林覆盖产品。该方法的主要特点在于针对青藏高原复杂的地表环境和植被类型,优化了随机森林模型的参数和训练特征,提高了模型的精度和泛化能力。精度验证结果表明,本产品的总体精度和Kappa系数分别为98.29%和0.9496,优于现有的ESA World Cover2020产品的95.04%和0.7712。本产品提供了青藏高原地区高精细度的森林覆盖信息,可为青藏高原森林资源管理、森林生态系统的碳储量和碳循环等研究提供基础数据。
