O'Toole Matthew, Lamoureux Phillip, Miller Kyle E
Department of Mathematics, Michigan State University, East Lansing, Michigan 48824-1115, USA.
Biophys J. 2008 Apr 1;94(7):2610-20. doi: 10.1529/biophysj.107.117424. Epub 2008 Jan 4.
Whether the axonal framework is stationary or moves is a central debate in cell biology. To better understand this problem, we developed a mathematical model that incorporates force generation at the growth cone, the viscoelastic properties of the axon, and adhesions between the axon and substrate. Using force-calibrated needles to apply and measure forces at the growth cone, we used docked mitochondria as markers to monitor movement of the axonal framework. We found coherent axonal transport that decreased away from the growth cone. Based on the velocity profiles of movement and the force applied at the growth cone, and by varying the attachment of the axonal shaft to the coverslip, we estimate values for the axial viscosity of the axon (3 x 10(6) +/- 2.4 x 10(6) Pa.s) and the friction coefficient for laminin/polyornithine-based adhesions along the axon (9.6 x 10(3) +/- 7.5 x 10(3) Pa.s). Our model suggests that whether axons elongate by tip growth or stretching depends on the level of force generation at the growth cone, the viscosity of the axon, and the level of adhesions along the axon.
轴突骨架是静止的还是移动的，这是细胞生物学中的一个核心争论点。为了更好地理解这个问题，我们开发了一个数学模型，该模型纳入了生长锥处的力产生、轴突的粘弹性以及轴突与底物之间的粘附。使用经过力校准的针在生长锥处施加和测量力，我们以对接的线粒体作为标记来监测轴突骨架的移动。我们发现连贯的轴突运输在远离生长锥处减少。基于移动的速度分布以及在生长锥处施加的力，并通过改变轴突轴与盖玻片的附着情况，我们估算出轴突的轴向粘度值（3×10⁶±2.4×10⁶帕·秒）以及沿轴突的基于层粘连蛋白/聚鸟氨酸的粘附的摩擦系数（9.6×10³±7.5×10³帕·秒）。我们的模型表明，轴突是通过顶端生长还是拉伸来延长，取决于生长锥处的力产生水平、轴突的粘度以及沿轴突的粘附水平。
