Departments of Neuroscience and Physiology, and Ophthalmology, State University of New York Upstate Medical University, Syracuse, New York, USA.
Biophys J. 2013 Jan 22;104(2):300-12. doi: 10.1016/j.bpj.2012.11.3835.
In vertebrate eyes, the rod photoreceptor has a modified cilium with an extended cylindrical structure specialized for phototransduction called the outer segment (OS). The OS has numerous stacked membrane disks and can bend or break when subjected to mechanical forces. The OS exhibits axial structural variation, with extended bands composed of a few hundred membrane disks whose thickness is diurnally modulated. Using high-resolution confocal microscopy, we have observed OS flexing and disruption in live transgenic Xenopus rods. Based on the experimental observations, we introduce a coarse-grained model of OS mechanical rigidity using elasticity theory, representing the axial OS banding explicitly via a spring-bead model. We calculate a bending stiffness of ∼10(5) nN⋅μm2, which is seven orders-of-magnitude larger than that of typical cilia and flagella. This bending stiffness has a quadratic relation to OS radius, so that thinner OS have lower fragility. Furthermore, we find that increasing the spatial frequency of axial OS banding decreases OS rigidity, reducing its fragility. Moreover, the model predicts a tendency for OS to break in bands with higher spring number density, analogous to the experimental observation that transgenic rods tended to break preferentially in bands of high fluorescence. We discuss how pathological alterations of disk membrane properties by mutant proteins may lead to increased OS rigidity and thus increased breakage, ultimately contributing to retinal degeneration.
在脊椎动物的眼睛中,杆状光感受器的纤毛经过修饰,具有延伸的圆柱形结构,专门用于光转导,称为外节(OS)。OS 有许多堆叠的膜盘,当受到机械力时可以弯曲或断裂。OS 表现出轴向结构变化,具有由几百个膜盘组成的扩展带,其厚度随昼夜节律调节。使用高分辨率共聚焦显微镜,我们观察到活的转基因非洲爪蟾杆状细胞中的 OS 弯曲和破坏。基于实验观察,我们使用弹性理论引入了 OS 机械刚性的粗粒模型,通过弹簧珠模型明确表示轴向 OS 带。我们计算出的弯曲刚度约为 10(5) nN⋅μm2,比典型的纤毛和鞭毛大七个数量级。这种弯曲刚度与 OS 半径呈二次关系,因此较薄的 OS 具有较低的脆性。此外,我们发现增加轴向 OS 带的空间频率会降低 OS 的刚性,从而降低其脆性。此外,该模型预测 OS 有在具有较高弹簧数密度的带中破裂的趋势,类似于实验观察到的转基因杆状细胞倾向于优先在高荧光带中破裂的情况。我们讨论了突变蛋白对盘膜性质的病理改变如何导致 OS 刚性增加,从而导致更多的断裂,最终导致视网膜变性。