The Properties of Chondrocyte Membrane Reservoirs and Their Role in Impact-Induced Cell Death
The Properties of Chondrocyte Membrane Reservoirs and Their Role in Impact-Induced Cell Death
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DOI：
10.1016/j.bpj.2013.08.035
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发表时间：
2013-10-01
影响因子：
3.4
通讯作者：
Herzog, Walter
中科院分区：
文献类型：
--
作者：
Moo, Eng Kuan;Amrein, Matthias;Herzog, Walter
关节软骨的冲击载荷导致软骨细胞广泛死亡。细胞膜的弹性范围有限，为 3-4% 应变，但在生理负荷期间，细胞膜通过其膜库（一种复杂的膜折叠模式）防止直接拉伸。使用有限元模型，我们之前提出，进入膜库的能力取决于应变率，并且在冲击载荷期间，可进入的膜库急剧减少，因此施加到软骨细胞的应变直接转移到细胞膜，当应变超过 3-4% 时，细胞膜就会失效。然而，该提议缺乏实验支持。本研究的目的是使用原子力显微镜的膜束缚技术测量不同膜应变率下可接近的膜库尺寸。我们对分离的软骨细胞 (n = 87) 进行了原子力谱分析。使用微米大小的悬臂以恒定的拉速从细胞表面提取膜系链。膜系链可以被识别为所得力-位移曲线中的力平台。测试了六种拉伸速率（1、5、10、20、40 和 80 μm/s）。膜储存器的尺寸（以膜系链表面积表示）随着牵引速率的增加而呈指数减小。目前的结果支持我们的理论发现，即暴露于冲击载荷的软骨细胞由于高张力膜应变率引起的膜破裂而死亡。
Impact loading of articular cartilage causes extensive chondrocyte death. Cell membranes have a limited elastic range of 3-4% strain but are protected from direct stretch during physiological loading by their membrane reservoir, an intricate pattern of membrane folds. Using a finite-element model, we suggested previously that access to the membrane reservoir is strain-rate-dependent and that during impact loading, the accessible membrane reservoir is drastically decreased, so that strains applied to chondrocytes are directly transferred to cell membranes, which fail when strains exceed 3-4%. However, experimental support for this proposal is lacking. The purpose of this study was to measure the accessible membrane reservoir size for different membrane strain rates using membrane tethering techniques with atomic force microscopy. We conducted atomic force spectroscopy on isolated chondrocytes (n = 87). A micron-sized cantilever was used to extract membrane tethers from cell surfaces at constant pulling rates. Membrane tethers could be identified as force plateaus in the resulting force-displacement curves. Six pulling rates were tested (1, 5, 10, 20, 40, and 80 mu m/s). The size of the membrane reservoir, represented by the membrane tether surface areas, decreased exponentially with increasing pulling rates. The current results support our theoretical findings that chondrocytes exposed to impact loading die because of membrane ruptures caused by high tensile membrane strain rates.