Zi Chen, PhD
Xiru Fan, Cristian Valenzuela, Weijing Zhao, Zi Chen*, Dong Wang, Steven J. Mentzer
Steven J. Mentzer
In the normal lung, the dominant cable is an elastic “line element” composed of elastin fibers bound to a protein scaffold. The cable line element maintains alveolar geometry by balancing surface forces within the alveolus and changes in lung volume with exercise. Recent work in the postnatal rat lung has suggested that the process of cable development is self-organized in the extracellular matrix. However, it remains poorly understood how tropoelastin spheres self-assemble into helical cable lines. Experiments show that early in postnatal development, a blanket of tropoelastin (TE) spheres appear in the primitive lung. Within 7 to 10 days, the TE spheres are incorporated into a distributed protein scaffold to create the mature cable line element. To study the process of extracellular assembly, we used cellular automata (CA) simulations. The simulations demonstrated that the intermediate step of tropoelastin self-aggregation into TE spheres enhanced the efficiency of cable formation more than 5-fold. Similarly, the rate of tropoelastin production had a direct impact on the efficiency of scaffold binding. The binding affinity of the tropoelastin to the protein scaffold, potentially reflecting heritable traits, also had a significant impact on cable development. In contrast, the spatial distribution of TE monomer production, increased Brownian motion and variations in scaffold geometry did not significantly impact cable development. Our study illustrates the impact of tropoelastin spheres concentration, geometry, and movement on the fundamental process of elastogenesis, and will shed light on the biophysical mechanism of the critical process of elastin fiber formation in living organisms and regenerative medicine.
Clinically, the possibility of the self-organized development of the cable line element in the lungs provides a new focus for studies of bronchopulmonary dysplasia and ventilator-induced lung injury.