Molecular Cell Biomechanics Laboratory, Department of Bioengineering, University of California, Berkeley, California, USA.
Biophys J. 2012 Feb 22;102(4):749-57. doi: 10.1016/j.bpj.2011.11.4024. Epub 2012 Feb 21.
Microtubule bundles cross-linked by tau protein serve a variety of neurological functions including maintaining mechanical integrity of the axon, promoting axonal growth, and facilitating cargo transport. It has been observed that axonal damage in traumatic brain injury leads to bundle disorientation, loss of axonal viability, and cognitive impairment. This study investigates the initial mechanical response of axonal microtubule bundles under uniaxial tension using a discrete bead-spring representation. Mechanisms of failure due to traumatic stretch loading and their impact on the mechanical response and stability are also characterized. This study indicates that cross-linked axonal microtubule bundles in tension display stiffening behavior similar to a power-law relationship from nonaffine network deformations. Stretching of cross-links and microtubule bending were the primary deformation modes at low stresses. Microtubule stretch was negligible up to tensile stresses of ∼1 MPa. Bundle failure occurred by failure of cross-links leading to pull-out of microtubules and loss of bundle integrity. This may explain the elongation, undulation, and delayed elasticity of axons following traumatic stretch loading. More extensively cross-linked bundles withstood higher tensile stresses before failing. The bundle mechanical behavior uncovered by these computational techniques should guide future experiments on stretch-injured axons.
微管束通过tau 蛋白交联，具有多种神经功能，包括维持轴突的机械完整性、促进轴突生长和促进货物运输。已经观察到创伤性脑损伤中的轴突损伤导致束定向紊乱、轴突活力丧失和认知障碍。本研究使用离散的珠子-弹簧表示法研究了单轴拉伸下轴突微管束的初始力学响应。还研究了由于创伤性拉伸加载导致的失效机制及其对力学响应和稳定性的影响。本研究表明，受拉的交联轴突微管束表现出类似于非仿射网络变形的幂律关系的硬化行为。在低应力下，交联和微管弯曲是主要的变形模式。微管拉伸在拉伸应力约为 1 MPa 时可以忽略不计。束的失效是由于交联失效导致微管拔出和束完整性丧失。这可能解释了创伤性拉伸加载后轴突的伸长、波动和延迟弹性。交联更广泛的束在失效前能承受更高的拉伸应力。这些计算技术揭示的束力学行为应指导对拉伸损伤轴突的进一步实验研究。
