Shape matters in protein mobility within membranes

The lateral mobility of proteins within cell membranes is usually thought to be dependent on their size and modulated by local heterogeneities of the membrane. Experiments using single-particle tracking on reconstituted membranes demonstrate that protein diffusion is significantly influenced by the interplay of membrane curvature, membrane tension, and protein shape. We find that the curvature-coupled voltage-gated potassium channel (KvAP) undergoes a significant increase in protein mobility under tension, whereas the mobility of the curvature-neutral water channel aquaporin 0 (AQP0) is insensitive to it. Such observations are well explained in terms of an effective friction coefficient of the protein induced by the local membrane deformation.Brownian motion plays an essential role in biological processes. Since the pioneering experiments of Perrin (1), the observation of diffusing objects has emerged as a mean to extract the rheological properties of the surrounding medium or the probe particle size. The theoretical investigation of diffusion of proteins within membranes has been studied widely going back to P. G. Saffman and M. Delbrück (SD). They investigated the hydrodynamic drag acting on a membrane inclusion when the membrane is described as a 2D fluid sheet of viscosity embedded within a less viscous fluid of viscosity η (2). In this theory, the diffusion coefficient D₀ in the limit of a large viscosity contrast between the membrane and bulk fluid is given by:The length is the length scale over which flow is generated within the bilayer by the inclusion, k_BT is the thermal energy, and γ is Euler’s constant. This model predicts a logarithmic dependence of D₀ on the protein radius a_p, which has been confirmed for some in vitro experiments on membranes containing transmembrane proteins (see ref. 3 and references therein). In contrast, the experiments of Gambin et al. (4) showed significant deviations from the SD theory.A possible origin for the discrepancy observed by Gambin et al. (4) is the significant local membrane deformation due to the interaction between the inclusion and the lipid bilayer (5). Naji et al. suggested in ref. 6 that inclusions experience additional dissipation, either due to internal flows within the membrane or to additional fluid flows produced by the deformed membrane. This work triggered a number of theoretical studies investigating the coupling of inclusion proteins with the membrane that had been pioneered by the Seifert’s group (see ref. 7 and references therein). Such studies have systematically gone beyond the SD model by including additional effects (8–12). So far, a thorough verification of these ideas has not been attempted. To investigate the effect of the protein–lipid coupling on the protein mobility, we study its dependence on membrane tension, because this parameter affects the local membrane deformation.In this work, we compare the mobility of two transmembrane proteins with the same lateral size, aquaporin 0 (AQP0) and a voltage-gated potassium channel (KvAP), reconstituted in giant unilamellar vesicles (GUVs). Whereas AQP0 does not deform locally the bilayer, KvAP locally bends the membrane (13). Using single-particle tracking (SPT), we demonstrate that the curvature-coupled protein KvAP undergoes a significant increase in mobility under tension, whereas the mobility of the curvature-neutral water channel AQP0 is insensitive to it. This difference, which goes beyond the SD model, is explained by an approach that includes the interplay between membrane deformation and friction with the surrounding medium and within the bilayer. This is compelling evidence that the Brownian motion of a shaping-membrane protein is not simply dependent on the inclusion size but also related to the lateral extension of the deformed membrane patch, which depends on tension.     

Wanted: pediatric nephrologists! — why trainees are not choosing pediatric nephrology

A workforce crisis for many pediatric specialties, particularly nephrology, is due to growing retirement rates, attrition during training, and retention difficulties. To obtain specific information regarding pediatric nephrology trainee shortages, we administered two cross-sectional surveys to non-renal pediatric subspecialty fellows and pediatric nephrology program directors. We characterized the fellows' experiences with nephrology and the program directors' experiences with their fellows as well as their outcomes in the last 10 years. We analyzed responses from 531 non-renal fellows (14.4% response rate). Overall, 317 (60%) fellows rated nephrology as difficult, particularly women (65.4% vs. 49.5%, p?p?=?0.001). More men than women (24% vs. 8%, p?相似文献   

不同椎板减压范围对BioFlex系统生物力学的影响

【摘要】 目的：利用有限元方法分析比较不同椎板减压范围对脊柱动态内固定BioFlex系统生物力学的影响。方法：利用Mimics 10.01三维重建软件建立正常L3～L5几何模型并利用ProE逆向工程软件建立BioFlex系统几何模型,按临床术式进行组装并导入ANSYS Workbench 14.0有限元分析软件进行前处理建立四种L3～L5三维有限元模型：完整状态L3～L5模型（INT组）,L4-L5椎板减压+1/2关节突切除+Bioflex模型（MF-BF组）,L4-L5椎板减压+全关节突切除+Bioflex模型（TF-BF组）,L4-L5椎板减压+髓核摘除+Bioflex模型（D-BF组）;在各模型L3椎体的上表面以及上关节突的关节面轴向予1200N载荷和8Nm、8Nm、6Nm、4Nm力矩下模拟人体腰椎正常生理轴向载荷、前屈、后伸、侧弯和扭转,L5椎体的下表面及下关节突表面各节点六个方向自由度完全固定。测量各模型固定节段和邻近节段的活动度以及邻近节段的髓核间应力与关节突应力,并进行分析比较。结果：椎板减压并置入动态内固定Bioflex系统后,脊柱固定节段的活动度各减压组较INT组明显减小（P＜0.05）,其中TF-BF组前屈活动度减小幅度最大达77.2%,MF-BF组后伸、侧弯、旋转活动度减小幅度最大分别达37.4%、67.2%、83.1%;邻近节段的活动度各减压组较INT组增大（P＜0.05）,其中MF-BF组前屈活动度增大幅度最大达22.9%,TF-BF组后伸、侧弯活动度增大幅度最大分别达18.2%、32.1%,DF-BF组旋转活动度增大幅度最大达13.8%。不同状态下固定节段及邻近节段活动度MF-BF组、TF-BF组及D-BF组间波动幅度不大,两两比较差异无统计学意义（P＞0.05）。邻近节段关节突应力及髓核间应力各减压组较INT组明显增大（P＜0.05）,其中TF-BF组关节突应力在后伸、旋转活动时增大幅度最大分别达81.6%、77.3%,DF-BF组关节突应力在侧弯活动时增大幅度最大达60.5%,DF-BF组髓核间应力在前屈活动时增大幅度最大达46.6%,MF-BF组髓核间应力在后伸、侧弯、旋转活动时增大幅度最大分别达11.8%、63.5%、51.3%;邻近节段的关节突应力与髓核间应力在不同状态下各减压组间波动幅度不大,两两比较差异无统计学意义（P＞0.05）。结论：置入BioFlex系统后脊柱固定节段的活动度明显减小,邻近节段的活动度增大,固定与邻近节段活动度不随椎板减压范围的改变而明显改变;邻近节段关节突应力及髓核间应力明显增大,其大小不随椎板减压节段范围的改变而明显改变。     

人工电触觉反馈对手抓握力的影响

目的:为了给受试者提供触觉反馈来完成抓取力的闭环控制,提出各种方法和相应的控制策略,以探究触觉反馈对手抓握力的影响,为假肢手的研究提供参考。方法:主要根据动态系统的输出特性提出了四类考察变量(三种失败次数、完成时间、握力的均值和握力的标准差),以及稳定性、快速性和经济性指标,依据上述准则来比较基于经皮电刺激的触觉反馈和无反馈对于控制握力的影响。结果:对于三种失败次数,无反馈模式下的表现均高于触觉反馈模式,尤其是在由摔碎和捏碎引起的失败次数上,无反馈模式下的结果分别为4.3次和4.9次,而电触觉反馈模式下的结果仅为0.6次和0.5次。对于反映时间,无反馈模式下的受试者完成实验的时间为26.4s,而在电触觉反馈模式下,受试者仅用17.7s。在对6个物体的抓取中,电触觉反馈下的握力始终小于无反馈模式下的结果。触觉反馈模式下的等效握力的稳定性要高于无反馈模式下的结果。结论:经皮电刺激的触觉反馈在四类考察变量以及3种目标上均优于无反馈,提示经皮电刺激的触觉反馈对于假肢手握力控制的重要性。随着物体重量的增加,无反馈和经皮电刺激的触觉反馈下抓取力的经济性和稳定性差异逐渐的减小。     

磁力靶向传递SPIO标记的BMSC修复关节软骨缺损的研究进展

关节软骨缺损修复一直是国内外研究的热点与难点。骨髓间充质干细胞移植技术具有良好的应用前景,但干细胞靶向问题亟待解决。该文阐述干细胞靶向传递的新策略--磁力靶向传递技术,重点介绍该技术应用于修复关节软骨缺损的背景、优势及存在的技术难点,并对该技术的应用前景进行展望。     

上肢圆周运动及反馈仪对偏瘫患者的作用分析

目的：证实上肢圆周运动反馈仪在左、右侧肢体偏瘫评定和治疗中的作用.方法：选择正常人及左、右侧偏瘫患者各10例,均接受上肢圆周运动反馈仪测定,其中偏瘫患者均接受30min/d共1个月的仪器训练,训练结束后再次接受仪器测定,获取综合力向量值、时间、频率参数,与正常人进行比较.结果：左侧肢体偏瘫患者在三区的力向量均值、时间、频率与正常人比较差异有显著性意义（P＜0.05）,而右侧偏瘫患者力向量参数变化不明显（P＞0.05）;正常人和左侧偏瘫患者各区力向量均值在训练后均有明显改善（P＜0.05）.结论：上肢圆周运动反馈仪能客观反映左侧偏瘫患者的功能障碍和改善左侧偏瘫上肢综合运动能力.     

Longitudinal assessment of hepatic fibrosis in responders to direct‐acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods

Successful eradication of recurrent hepatitis C virus (HCV) infection following liver transplantation (HCV) improves graft survival. This study aimed at evaluation of hepatic fibrosis changes among long‐term responders to DAA therapy for recurrent HCV after liver transplantation using noninvasive methods. Patients with significant hepatic fibrosis (≥F2) who achieved SVR12 after treatment with DAAs for recurrent HCV were included (n = 52). Hepatic fibrosis status was assessed, noninvasively, by calculation of fibrosis‐4 score (FIB‐4) and Aspartate Aminotransferase Platelet Ratio Index (APRI) and by measurement of graft stiffness using FibroScan at baseline and 12 and 18 months post‐treatment. Acoustic radiation force imaging (ARFI) was done for all patients 12 and 18 months post‐treatment. Patients were classified into two groups based on baseline liver stiffness measurement (LSM) by FibroScan; significant fibrosis (F2; n = 28) and advanced fibrosis groups (≥F3). Over 18‐month follow‐up period, there was serial improvement of FIB‐4, APRI, and LSM by FibroScan in both groups. Higher baseline LSM and delayed initiation of antiviral therapy were significant predictors of lack of fibrosis regression (P‐value 0.01 and 0.04, respectively). Fibroindices and LSM improved over time in liver transplant recipients who responded to DAAs. Baseline LSM can predict post‐treatment fibrosis regression.