Nia Hadi Tavakoli, Han Lin, Bozchalooi Iman Soltani, Roughley Peter, Youcef-Toumi Kamal, Grodzinsky Alan J, Ortiz Christine
†Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
‡School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104, United States.
ACS Nano. 2015 Mar 24;9(3):2614-25. doi: 10.1021/nn5062707. Epub 2015 Mar 13.
Poroelastic interactions between interstitial fluid and the extracellular matrix of connective tissues are critical to biological and pathophysiological functions involving solute transport, energy dissipation, self-stiffening and lubrication. However, the molecular origins of poroelasticity at the nanoscale are largely unknown. Here, the broad-spectrum dynamic nanomechanical behavior of cartilage aggrecan monolayer is revealed for the first time, including the equilibrium and instantaneous moduli and the peak in the phase angle of the complex modulus. By performing a length scale study and comparing the experimental results to theoretical predictions, we confirm that the mechanism underlying the observed dynamic nanomechanics is due to solid-fluid interactions (poroelasticity) at the molecular scale. Utilizing finite element modeling, the molecular-scale hydraulic permeability of the aggrecan assembly was quantified (kaggrecan = (4.8 ± 2.8) × 10(-15) m(4)/N·s) and found to be similar to the nanoscale hydraulic permeability of intact normal cartilage tissue but much lower than that of early diseased tissue. The mechanisms underlying aggrecan poroelasticity were further investigated by altering electrostatic interactions between the molecule's constituent glycosaminoglycan chains: electrostatic interactions dominated steric interactions in governing molecular behavior. While the hydraulic permeability of aggrecan layers does not change across species and age, aggrecan from adult human cartilage is stiffer than the aggrecan from newborn human tissue.
组织间隙液与结缔组织细胞外基质之间的孔隙弹性相互作用对于涉及溶质运输、能量耗散、自我硬化和润滑的生物学及病理生理学功能至关重要。然而,纳米尺度下孔隙弹性的分子起源在很大程度上尚不清楚。在此,首次揭示了软骨聚集蛋白聚糖单层的广谱动态纳米力学行为,包括平衡模量和瞬时模量以及复模量相角中的峰值。通过进行长度尺度研究并将实验结果与理论预测进行比较,我们证实观察到的动态纳米力学背后的机制是由于分子尺度上的固液相互作用(孔隙弹性)。利用有限元建模,对聚集蛋白聚糖组装体的分子尺度水力渗透率进行了量化(kaggrecan = (4.8 ± 2.8) × 10(-15) m(4)/N·s),发现其与完整正常软骨组织的纳米尺度水力渗透率相似,但远低于早期病变组织的水力渗透率。通过改变分子组成的糖胺聚糖链之间的静电相互作用,进一步研究了聚集蛋白聚糖孔隙弹性的潜在机制:在控制分子行为方面静电相互作用主导空间相互作用。虽然聚集蛋白聚糖层得水力渗透率在不同物种和年龄之间没有变化,但来自成人软骨的聚集蛋白聚糖比来自新生儿组织的聚集蛋白聚糖更硬。