curvature

曲率
  • 文章类型: Journal Article
    最近,各种微环境生物物理刺激已被证明在调节细胞功能中起着至关重要的作用。其中,形态物理线索,像曲率,正在成为细胞行为的关键监管者。基板曲率的变化已被证明会影响焦点粘附(FA)的排列,影响细胞骨架的方向和强度会产生力,并导致细胞机械特性的整体改变。在他们的原生环境中,细胞遇到不同程度的基底曲率,在特定的器官中,由于周期性组织变形,它们暴露于曲率的动态变化。然而,细胞感知基底曲率的机制仍然知之甚少。为了这个目标,设计并实现了一种微气动装置。该装置能够控制基板曲率的应用,静态和动态。采用实验和模拟相结合的方法,人脂肪干细胞暴露于受控的曲率强度和频率.在这次曝光期间,对FA的延伸和取向进行了测量,细胞骨架组织和细胞/核排列。数据清楚地表明基底曲率对细胞粘附过程的显着影响。这些发现有助于更好地理解细胞感知和响应底物曲率信号的机制。重要声明:这项工作是我们对理解基底曲率功能的贡献,在粘着斑和细胞机械特性的尺度上,它是细胞粘附的关键调节剂。近年来,大量的知识正在不断增长,提供对各种微环境生物物理刺激在调节细胞功能中的作用的理解。然而,对基底曲率的作用知之甚少,特别是,当细胞以动态方式暴露于这种刺激时。为了解决基底曲率对细胞行为的作用,设计并实现了一种微气动装置。该装置能够控制基板曲率的应用,静态和动态。实验数据充分表明,底物曲率对细胞粘附的机制有重大影响。
    Recently, a variety of microenvironmental biophysical stimuli have been proved to play a crucial role in regulating cell functions. Among them, morpho-physical cues, like curvature, are emerging as key regulators of cellular behavior. Changes in substrate curvature have been shown to impact the arrangement of Focal Adhesions (FAs), influencing the direction and intensity of cytoskeleton generated forces and resulting in an overall alteration of cell mechanical identity. In their native environment, cells encounter varying degrees of substrate curvature, and in specific organs, they are exposed to dynamic changes of curvature due to periodic tissue deformation. However, the mechanism by which cells perceive substrate curvature remains poorly understood. To this aim, a micro-pneumatic device was designed and implemented. This device enables the controlled application of substrate curvature, both statically and dynamically. Employing a combined experimental and simulative approach, human adipose-derived stem cells were exposed to controlled curvature intensity and frequency. During this exposure, measurements were taken on FAs extension and orientation, cytoskeleton organization and cellular/nuclear alignment. The data clearly indicated a significant influence of the substrate curvature on cell adhesion processes. These findings contribute to a better understanding of the mechanisms through which cells perceive and respond to substrate curvature signals. STATEMENT OF SIGNIFICANCE: This work is our contribution to the comprehension of substrate curvature\'s function as a crucial regulator of cell adhesion at the scale of focal adhesions and cell mechanical identity. In recent years, a large body of knowledge is continuously growing providing comprehension of the role of various microenvironmental biophysical stimuli in regulating cell functions. Nevertheless, little is known about the role of substrate curvature, in particular, when cells are exposed to this stimulus in a dynamic manner. To address the role of substrate curvature on cellular behavior, a micro-pneumatic device was designed and implemented. This device enables the controlled application of substrate curvature, both statically and dynamically. The experiment data made it abundantly evident that the substrate curvature had a major impact on the mechanisms involved in cell adhesion.
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  • 文章类型: Journal Article
    硼使植物细胞壁中的RG-II二聚化,对植物细胞伸长至关重要。然而,由于RG-II突变体的严重表型或致死性,研究植物中的RG-II二聚化具有挑战性。硼剥夺消除了RG-II二聚化和植物生长,但这些表型是否或如何在功能上关联仍不清楚.硼酸类似物可以作为实验工具来干扰RG-II交联。这里,我们研究了用硼酸类似物处理的拟南芥幼苗中的RG-II二聚化和发育表型,苯基硼酸(PBA),测试观察到的发育表型是否归因于RG-II二聚化的改变或植物中硼的其他推定功能。我们发现PBA处理改变了幼苗的根系发育,而RG-II二聚化和分布不受影响。令人惊讶的是,在低硼条件下,PBA处理i)对根大小没有影响,但仍阻止侧根发育,ii)恢复RG-II二聚化。PBA处理也破坏了生长素水平,可能解释了用这种类似物处理的幼苗中不存在侧根。我们得出结论,PBA与RG-II和其他细胞靶标如生长素信号传导成分相互作用,由PBA引起的表型来自对硼多种功能的干扰。
    Boron dimerizes RG-II in the plant cell wall and is crucial for plant cell elongation. However, studying RG-II dimerization in plants is challenging because of the severe phenotypes or lethality of RG-II mutants. Boron deprivation abrogates both RG-II dimerization and plant growth, but whether or how these phenotypes are functionally linked has remained unclear. Boric acid analogues can serve as experimental tools to interfere with RG-II cross-linking. Here, we investigated RG-II dimerization and developmental phenotypes in Arabidopsis thaliana seedlings treated with a boric acid analogue, phenylboronic acid (PBA), to test whether the observed developmental phenotypes are attributable to alteration of RG-II dimerization or to other putative functions of boron in plants. We found that PBA treatment altered root development in seedlings while RG-II dimerization and distribution were not affected. Surprisingly, under low boron conditions, PBA treatment i) had no effect on root size but still prevented lateral root development and ii) restored RG-II dimerization. PBA treatment also disrupted auxin levels, potentially explaining the absence of lateral roots in seedlings treated with this analogue. We conclude that PBA interacts both with RG-II and other cellular targets such as auxin signaling components, and that the phenotypes caused by PBA arise from interference with multiple functions of boron.
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  • 文章类型: Journal Article
    简介:几十年来,扫视系统一直是神经生理学家最喜欢的目标,寻求阐明眼球运动的神经控制,部分是因为扫视的特点是一组高度刻板的振幅之间的关系,持续时间,和峰值速度。有大量文献描述了正常灵长类动物中这些运动的动力学和轨迹,但是对于婴儿斜视综合征的受试者没有类似的详细分析。先前的研究表明,在这种疾病中,双眼扫视的幅度和方向通常不同,但目前尚不清楚是否存在类似的矛盾。本研究旨在确定双眼斜视的扫视持续时间是否不同,以及是否存在涉及这些运动轨迹的异常。方法:对两只正常猴子进行扫视轨迹和持续时间的动态分析,两个患有内斜视,两个患有外斜视。比较了两只眼睛的弯曲量。对于每只斜视的猴子,将弯曲量与正常对照进行比较。扫视被放入12个垃圾箱,基于方向;对于每个垃圾箱,比较了两只眼睛的平均扫视持续时间(持续时间不一致)。然后比较了斜视猴子的每个bin的持续时间错位,与正常对照动物相比。结果:令人惊讶的是,在患有模式斜视的受试者中,弯曲量并不总是更大。然而,对于所有患有斜视的猴子,双眼的扫视曲率差异明显更大,与正常对照相比。此外,对于斜视受试者的扫视子集,两只眼睛的扫视持续时间相差超过10ms,即使动物完全警觉.讨论:据作者所知,这是第一项研究表明,在斜视中,双眼的扫视持续时间可能会有异常大的差异。这些数据也表明,在有斜视图案的猴子身上,脑干中异常的水平-垂直串扰可导致定向失调,而不会显着损害分量拉伸。这些结果对未来尝试对导致模式斜视定向失调的神经机制进行建模的尝试施加了重要限制。
    Introduction: For decades, the saccadic system has been a favorite target of neurophysiologists seeking to elucidate the neural control of eye movements, partly because saccades are characterized by a set of highly stereotyped relationships between amplitude, duration, and peak velocity. There is a large literature describing the dynamics and trajectories of these movements in normal primates, but there are no similarly detailed analyses for subjects with infantile strabismus syndrome. Previous studies have shown the amplitudes and directions of saccades often differ for the two eyes in this disorder, but it is unknown whether a similar disconjugacy exists for duration. The present study was designed to determine whether or not saccade duration differs for the two eyes in strabismus, and whether there are abnormalities involving the trajectories of these movements. Methods: Dynamic analyses of saccade trajectories and durations were performed for two normal monkeys, two with esotropia and two with exotropia. The amount of curvature was compared for the two eyes. For each monkey with strabismus, the amount of curvature was compared to normal controls. Saccades were placed into 12 bins, based on direction; for each bin, the mean saccade duration was compared for the two eyes (duration disconjugacy). The duration disconjugacy for each bin was then compared for monkeys with strabismus, versus normal control animals. Results: Surprisingly, the amount of curvature was not consistently greater in subjects with pattern strabismus. However, saccade curvature differed for the two eyes by a significantly greater amount for all monkeys with strabismus, compared to normal controls. In addition, for a subset of saccades in subjects with strabismus, saccade duration differed for the two eyes by more than 10 ms, even when the animal was fully alert. Discussion: To the best of the author\'s knowledge, this is the first study to show that, in strabismus, saccade durations can differ for the two eyes by an abnormally large amount. These data also suggest that, in monkeys with pattern strabismus, abnormal horizontal-vertical crosstalk in brainstem can lead to directional disconjugacy without significantly impairing component stretching. These results place important constraints on future attempts to model the neural mechanisms that contribute to directional disconjugacy in pattern strabismus.
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  • 文章类型: Journal Article
    对于RRT*算法,存在诸如更大的随机性之类的问题,较长时间的消费,更多的冗余节点,以及在自动驾驶车辆的路径规划过程中遇到未知障碍物时无法进行局部避障。而应用于自动驾驶汽车的人工势场法(APF)容易出现局部最优性、无法到达的目标,以及对全球场景的不适用性。提出了一种将改进的RRT*算法与改进的人工势场法相结合的融合算法。首先,对于RRT*算法,介绍了人工势场的概念和概率抽样优化策略,根据道路曲率设计自适应步长。对规划的全局路径进行路径后处理,减少生成路径的冗余节点,提高抽样的目的,解决在目标点附近扩展时可能发生振荡的问题,减少RRT*节点采样的随机性,提高路径生成效率。其次,对于人工势场法,通过设计避障约束,增加道路边界斥力势场,优化排斥函数和安全椭圆,无法达到目标的问题可以解决,可以减少路径中不必要的转向,可以提高规划路径的安全性。面对U形障碍,生成虚拟重力点来解决局部最小问题,提高障碍物的通过性能。最后,融合算法,结合改进的RRT*算法和改进的人工势场法,是设计的。前者首先规划了全球道路,提取路径节点作为后者的临时目标点,引导车辆行驶,当遇到未知障碍物时,通过改进的人工势场法避开局部障碍物,然后平滑融合算法规划的路径,使路径满足车辆运动学约束。在不同道路场景下的仿真结果表明,本文提出的方法能够快速规划出更加稳定的平滑路径,更准确,适合车辆驾驶。
    For the RRT* algorithm, there are problems such as greater randomness, longer time consumption, more redundant nodes, and inability to perform local obstacle avoidance when encountering unknown obstacles in the path planning process of autonomous vehicles. And the artificial potential field method (APF) applied to autonomous vehicles is prone to problems such as local optimality, unreachable targets, and inapplicability to global scenarios. A fusion algorithm combining the improved RRT* algorithm and the improved artificial potential field method is proposed. First of all, for the RRT* algorithm, the concept of the artificial potential field and probability sampling optimization strategy are introduced, and the adaptive step size is designed according to the road curvature. The path post-processing of the planned global path is carried out to reduce the redundant nodes of the generated path, enhance the purpose of sampling, solve the problem where oscillation may occur when expanding near the target point, reduce the randomness of RRT* node sampling, and improve the efficiency of path generation. Secondly, for the artificial potential field method, by designing obstacle avoidance constraints, adding a road boundary repulsion potential field, and optimizing the repulsion function and safety ellipse, the problem of unreachable targets can be solved, unnecessary steering in the path can be reduced, and the safety of the planned path can be improved. In the face of U-shaped obstacles, virtual gravity points are generated to solve the local minimum problem and improve the passing performance of the obstacles. Finally, the fusion algorithm, which combines the improved RRT* algorithm and the improved artificial potential field method, is designed. The former first plans the global path, extracts the path node as the temporary target point of the latter, guides the vehicle to drive, and avoids local obstacles through the improved artificial potential field method when encountered with unknown obstacles, and then smooths the path planned by the fusion algorithm, making the path satisfy the vehicle kinematic constraints. The simulation results in the different road scenes show that the method proposed in this paper can quickly plan a smooth path that is more stable, more accurate, and suitable for vehicle driving.
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  • 文章类型: Journal Article
    已提出同心管机器人(CTR)在非结构化环境中进行微创手术。在这封信中,我们考虑管道在通道内部以较大间隙或较大曲率行进的操作场景,如主动脉或工业管道。在这些操作场景中开发运动计划和控制需要对CTR进行精确的运动学建模。为此,我们将传统的CTR运动学模型扩展到具有较大的管间间隙和较大的中心线曲率的更一般的情况。进行了数值模拟和实验验证,以将我们的模型与传统的CTR运动学模型进行比较。在物理实验中,我们提出的模型在2D刨床情况下实现了1.53mm的尖端位置误差,在3D情况下实现了3.86mm的尖端位置误差,比最先进的模型高出71%和61%,分别。
    Concentric Tube Robots (CTRs) have been proposed to operate within the unstructured environment for minimally invasive surgeries. In this letter, we consider the operation scenario where the tubes travel inside the channels with a large clearance or large curvature, such as aortas or industrial pipes. Accurate kinematic modeling of CTRs is required for the development of motion planning and control within these operation scenarios. To this end, we extended the conventional CTR kinematics model to a more general case with large tube-to-tube clearance and large centerline curvature. Numerical simulations and experimental validations are conducted to compare our model with respect to the conventional CTR kinematic model. In the physical experiments, our proposed model achieved a tip position error of 1.53 mm in the 2D planer case and 3.86 mm in 3D case, outperforming the state-of-the-art model by 71% and 61%, respectively.
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  • 文章类型: Journal Article
    评估飞秒激光辅助原位角膜磨镶术(FS-LASIK)和经上皮屈光角膜切削(Trans-PRK)术后近视患者不同区域的曲率变化及其与角膜上皮重塑的相关性。
    使用眼前节光学相干断层扫描(OCT)测量上皮厚度和角膜地形图以测量不同区域的角膜曲率(2mm,5mm,和7毫米)。我们计算曲率ΔK(ΔK=术前-术后),ΔK5-2(ΔK5-2=K5mm-K2mm),ΔK7-5(ΔK7-5=K7mm-K5mm),和上皮厚度ΔET5-2(ΔET5-2=ET5mm-ET2mm)和ΔET7-5(ΔET7-5=ET7mm-ET5mm)。
    两组每个区域的角膜曲率变平(均p<0.001),并在随访期间逐渐变陡。Trans-PRK组在2mm和5mm内变平更明显,而FS-LASIK组为7mm。两组的ΔK随时间降低。两组的ΔK5-2和ΔK7-5在随访期间逐渐降低(Trans-PRK的P5-2=0.025和P7-5<0.001,对于FS-LASIK,P5-2=0.011和P7-5<0.001)。两组患者在随访期间角膜上皮逐渐增厚,Trans-PRK在中央和周围区域明显增厚,在中央和中央旁区域明显增厚。ΔK5-2和ΔET5-2、ΔK7-5和ΔET7-5之间存在显著相关性(均r>0.37,p<0.001)。
    所有组术后均显示出显着的曲率平坦化,并在随访期间逐渐陡峭化。两组17个区域的角膜上皮厚度变厚,.相比之下,Trans-PRK组显示FS-LASIK的外周和中心5mm区域更明显的增厚。这项研究表明,不同区域的上皮增厚差异与相应区域PRK的曲率变化差异之间存在显着正相关,FS-LASIK,曲率,角膜上皮厚度。
    UNASSIGNED: To evaluate curvature changes in different regions and their correlation with corneal epithelial remodeling in myopic patients undergoing femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and transepithelial refractive keratectomy (Trans-PRK) after surgery.
    UNASSIGNED: One hundred and sixty-three patients (163 right eyes) undergoing Trans-PRK and LASIK were evaluated for up to 6 months using anterior segment optical coherence tomography (OCT) to measure the epithelial thickness and corneal topography to measure corneal curvature in different areas (2 mm, 5 mm, and 7 mm). We calculated the curvature ΔK (ΔK = preoperative - postoperative), ΔK5-2 (ΔK5-2 = K5mm - K2mm), ΔK7-5 (ΔK7-5 = K7mm - K5mm), and the epithelial thickness ΔET5-2 (ΔET5-2 = ET5mm - ET2mm) and ΔET7-5 (ΔET7-5= ET7mm - ET5mm).
    UNASSIGNED: Corneal curvature flattened in each region of the two groups (all p < 0.001) and gradually steepened during the follow-up period. The Trans-PRK group flattened more significantly within 2 mm and 5 mm, while the FS-LASIK group at 7 mm. Both groups of ΔK decreased over time. Both groups of ΔK5-2 and ΔK7-5 gradually decreased during the follow-up period (P5-2=0.025 and P7-5 < 0.001 for Trans-PRK, P5-2 = 0.011 and P7-5 < 0.001 for FS-LASIK). The corneal epithelium of the two groups gradually thickened during the follow-up period, with Trans-PRK significantly thickening in the central and peripheral regions and FS-LASIK in the central and paracentral regions. There is a significant correlation between the ΔK5-2 and ΔET5-2, ΔK7-5 and ΔET7-5 (all r > 0.37, p < 0.001).
    UNASSIGNED: All groups showed significant curvature flattening after surgery and gradually steepening during the follow-up period. The corneal epithelium thickness in both groups of 17 regions became thicker,. In contrast, Trans-PRK group showed more significant thickening to the periphery and the central 5 mm area of the FS-LASIK. This study indicates a significant positive correlation between differences in epithelial thickening in different regions and differences in curvature changes in the corresponding areas PRK, FS-LASIK, curvature, corneal epithelial thickness.
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  • 文章类型: Journal Article
    背景:肾盂骨丢失被认为是复发性前肩关节不稳的重要危险因素。本研究的目的是开发一种准确且可重复的方法,用于量化肩关节前不稳定患者的骨丢失。
    方法:共采集了66组关节盂的计算机断层扫描图像,并建立了正面视图。根据关节盂下半部和后下象限的轮廓,使用最小二乘法绘制最佳拟合圆,并比较半径.骨丢失是通过模拟截骨术产生的,并开发了一种基于后下象限轮廓的骨丢失估计方法。
    结果:基于关节盂的下半部和后下象限,最佳拟合圆的半径分别为29.30±1.84mm和33.76±2.04mm,分别为(P<0.01)。采用模拟截骨的下半或后下象限的轮廓进行骨丢失定量,差异有统计学意义(P<0.01)。对于25%的关节盂骨丢失,使用传统方法对后下象限轮廓的估计值为34%。根据关节盂后下象限的轮廓,开发了一种准确定量骨丢失的新方法。
    结论:由于下半部和下半部的曲率半径不同,基于后下象限边缘的关节盂骨丢失估计可能会高估关节盂骨丢失。开发了一种数学方法来纠正此错误,并可能有助于使用肩关节前不稳定患者的后下象限的轮廓更准确地测量关节盂骨丢失。
    BACKGROUND: Glenoid bone loss is proposed to be an important risk factor for recurrent anterior shoulder instability. The purpose of the present study was to develop an accurate and reproducible method for quantifying a bone loss in patients with anterior shoulder instability.
    METHODS: A total of 66 sets of computed tomography images of the glenoid were acquired and en face view was established. Based on the contour of the inferior half and posteroinferior quadrant of the glenoid, the best-fit circle was drawn using the least-squares method with a comparison of the radii. A bone loss was created via a simulated osteotomy, and a method for estimating the bone loss based on the contour of the posteroinferior quadrant was developed.
    RESULTS: The radii of the best-fit circle were 29.30±1.84 mm and 33.76±2.04 mm based on the inferior half and posteroinferior quadrant of the glenoid, respectively (P<0.01). Bone loss quantification using the contour of the inferior half or posteroinferior quadrant with simulated osteotomy showed a significant difference (P<0.01). For a 25% of glenoid bone loss, the estimated value using the traditional method on the contour of the posteroinferior quadrant was 34%. the A new method for accurate bone loss quantification was developed based on the contour of the posteroinferior quadrant of the glenoid.
    CONCLUSIONS: Estimation of the glenoid bone loss based on the rim of the posteroinferior quadrant may overestimate the glenoid bone loss due to the difference in the radius of the curvature of the inferior half and posteroinferior quadrant. A mathematical method was developed to correct this error and may aid in more accurately measuring the glenoid bone loss using the contour of the posteroinferior quadrant in patients with anterior shoulder instability.
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  • 文章类型: Journal Article
    石竹目中许多物种的种子都表现出称为结节的表面突起。虽然结节的形状和分布经常被提出作为分类学标准,矛盾的是,他们的描述主要依靠形容词,有结节宽度的定量数据,高度,以及文献中缺乏的其他测量。最近,基于结节宽度的种子表面结节的定量分析,高度,和曲率值(最大和平均曲率,和最大平均曲率比)被提出并应用于总共31种的个体种群,12个属于SileneSubg.Behenantha和19到S.subg。Silene.结节被分为两类:棘突和皱纹。回声结节表现出更高的高度和曲率值,和较低的宽度,在S.subg物种中更为普遍。Behenantha,而S.subg中的rugose类型更为丰富。Silene.这项工作探索了结节大小和形状的特异性差异。为此,结节宽度的测量,将高度和曲率应用于8种硅烯的31个种群。对于大多数检查的物种,观察到种群之间的显着差异。一种特殊的结节类型,以前描述为脐带或乳头状,在夜蛾种子中发现,具有高曲率值的特点。
    The seeds of many species in the order Caryophyllales exhibit surface protuberances called tubercles. While tubercle shape and distribution have often been proposed as taxonomic criteria, paradoxically, their description has primarily relied on adjectives, with quantitative data on tubercle width, height, and other measurements lacking in the literature. Recently, a quantitative analysis of seed surface tubercles based on tubercle width, height, and curvature values (maximum and average curvature, and maximum to average curvature ratio) was proposed and applied to individual populations of a total of 31 species, with 12 belonging to Silene subg. Behenantha and 19 to S. subg. Silene. Tubercles were classified into two categories: echinate and rugose. Echinate tubercles exhibited higher values of height and curvature, and lower width, and were more prevalent in species of S. subg. Behenantha, while the rugose type was more abundant in S. subg. Silene. This work explored infraspecific differences in tubercle size and shape. For this, measurements of tubercle width, height and curvature were applied to 31 populations of eight species of Silene. Significant differences between populations were observed for most of the species examined. A particular tubercle type, previously described as umbonate or mammillate, was identified in S. nocturna seeds, characterized by high curvature values.
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  • 文章类型: Journal Article
    细胞外囊泡(EV),运输不同的细胞成分,在许多生理和病理过程中,在细胞间通讯中起着至关重要的作用。EV也被认为是用于治疗目的和无细胞再生医学的药物递送平台。虽然各种方法都集中在增加电动汽车产量,以有效使用电动汽车的治疗用途,提高电动汽车的质量,例如确保靶细胞的有效摄取,尚未被广泛探索。在这项研究中,我们将负膜曲率形成反向BAR(IBAR)结构域与整合素β尾结合滑石F3结构域连接,以创建IBAR-F3融合蛋白。我们观察到IBAR-F3可以触发丝状类膜突起,并将整合素吸引到那些富含突起的区域,当在表达整合素αIIbβ3的中国仓鼠卵巢细胞中表达时。令人惊讶的是,IBAR-F3的表达也诱导了电动汽车的强劲产生,然后被附近细胞以整合素依赖性方式有效吸收。此外,IBAR触发整合素激活,推测是通过诱导可能破坏整合素α和β跨膜结构域之间的相互作用的负膜曲率。因此,我们建议IBAR-F3应用于促进EV的产生和整合素介导的有效摄取。此外,负曲率诱导的整合素激活表明,电动汽车上的整合素可以通过电动汽车曲率的纳米级变化来激活,而无需常规机械来激活电动汽车内的整合素。
    Extracellular vesicles (EVs), transporting diverse cellular components, play a crucial role in intercellular communication in numerous physiological and pathological processes. EVs have also been recognized as a drug delivery platform for therapeutic purposes and cell-free regenerative medicine. While various approaches have focused on increasing EV production for efficient use therapeutic use of EVs, enhancing the quality of EVs, such as ensuring efficient uptake by their target cells, has not been widely explored. In this study, we linked a negative membrane curvature-forming inverse BAR (IBAR) domain with an integrin β tail-binding talin F3 domain to create the IBAR-F3 fusion protein. We observed that IBAR-F3 can trigger filopodia-like membrane protrusions and attract integrins to those protrusion-rich regions, when expressed in Chinese hamster ovary cells expressing integrin αIIbβ3. Surprisingly, the expression of IBAR-F3 also induced a robust production of EVs, which were then efficiently taken up by nearby cells in an integrin-dependent manner. Moreover, IBAR triggered integrin activation, presumably by inducing negative membrane curvature that likely disrupts the interaction between the integrin α and β transmembrane domain. Therefore, we suggest that IBAR-F3 should be utilized to promote both EV production and efficient uptake mediated by integrins. Furthermore, the negative curvature-inducing integrin activation suggests that integrins on EVs can be activated by the nanoscale change in the curvature of the EV without the need for conventional machinery to activate integrin inside the EVs.
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  • 文章类型: Journal Article
    病理组织内间质液压力(IFP)升高(例如,肿瘤,肾脏阻塞,和肝硬化肝脏)对纳米药物的运输产生了重大阻碍,最终损害治疗效率。在这些组织中,实体肿瘤是最具挑战性的情况。虽然已经设计了几种通过减少肿瘤IFP来增强纳米颗粒递送的策略,很少有方法专注于调节纳米粒子的固有特性,以有效地抵消外渗和渗透过程中的IFP,正是被升高的IFP阻碍的阶段。在这里,我们提出了一种创新的解决方案,通过设计具有高曲率梭形形状的纳米粒子,在肿瘤组织内的外渗和渗透期间,能够有效克服IFP屏障。通过实验和理论分析,我们证明,具有最高平均曲率的细长纳米粒子优于球形和杆状对应物,导致优越的肿瘤内积累和抗肿瘤疗效。超分辨率显微镜和分子动力学模拟揭示了高曲率有助于在外渗过程中克服高压差的阻力减小的潜在机制。同时,促进的旋转运动增加了穿透期间的跳频。这项研究有效地解决了高压障碍带来的局限性,揭示纳米粒子的物理特性与环境之间的相互作用,并提出了通过纳米医学推进癌症治疗的有希望的途径。
    Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod-shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Super-resolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high-pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high-pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine.
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