Extracellular Assembly of the Elastin Cable Line Element in the Developing Lung

Valenzuela, Cristian D.; Wagner, Willi L.; Bennett, Robert D.; Ysasi, Alexandra B.; Belle, Janeil; Molter, Karin; Straub, Beate K.; Wang, Dong; Chen, Zi; Ackermann, Maximilian; Tsuda, Akira; Mentzer, Steven J.

doi:10.1002/ar.23603

Cited by 8 publications

(16 citation statements)

References 35 publications

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“…The average size of the TE spheres decreased as the available TE monomers were bound. The efficiency of TE binding to the protein scaffold suggested an 800-time step process interval; that is, a time interval compatible with the experimental observations of 8-10 days for the development of the mature cable [10]. Importantly, if TE monomers did not aggregate into TE spheres-and the process relied upon TE monomer binding alone-the formation of the cable line element required more than 45 days.…”

Section: Elastin Aggregation and Protein Bindingsupporting

confidence: 70%

Stochastic simulations of self-organized elastogenesis in the developing lung

et al. 2023

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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. 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 creating the mature cable line element. To study the process of extracellular assembly, we used cellular automata (CA) simulations. CA 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 simulations of cable development. We conclude that CA simulations are useful in exploring the impact of concentration, geometry, and movement on the fundamental process of elastogenesis.

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Section: Elastin Aggregation and Protein Bindingsupporting

confidence: 70%

Stochastic simulations of self-organized elastogenesis in the developing lung

et al. 2023

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“…Studies on alveolarization generally rely on the identification and validation of pathways that direct lung development, using pharmacological and genetic approaches. Small‐molecule and proteinaceous modulators of developmental pathways have been administered via the enteral or parenteral routes, and subsequently, the impact on the development of the lung structure might be assessed microscopically (Valenzuela et al, ) or radiologically (Xiao et al, ); alongside screens for transcriptomic changes (Mariani, ), by microarray, or more recently, RNA‐Seq (Bhattacharya et al, ; Lingappan et al, ) technology. Small‐molecule interventions have, in the past, relied on enzyme inhibitors to block enzyme function (Reviewed in Madurga et al, ; Silva et al, ; Surate Solaligue et al, ); but have recently been expanded to include chemical chaperones (Nguyen and Uhal, ; Siddesha et al, ) and genetic interference, through sequence‐specific modulation of microRNA function using antagomiRs (Nardiello and Morty, ) or microRNA mimics (Olave et al, ; Durrani‐Kolarik et al, ).…”

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confidence: 99%

Control Interventions Can Impact Alveolarization and the Transcriptome in Developing Mouse Lungs

Fehl

Pozarska

Nardiello

et al. 2018

The Anatomical Record

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There is currently much interest in understanding the mechanisms of normal and aberrant lung alveolarization, particularly in the context of bronchopulmonary dysplasia, a common complication of preterm birth where alveolarization is impeded. To this end, the parenteral administration of pharmacological agents that modulate biochemical pathways, or facilitate modulation of gene expression in transgenic animals, has facilitated the discovery and validation of mechanisms that direct lung development. Such studies include control interventions, where the solvent vehicle, perhaps containing an inactive form of the agent applied, is administered; thereby providing a well-controlled point of reference for the analysis of the partner experiment. In the present study, the impact of several widely used control interventions in developing C57Bl/6J mouse pups was examined for effects on lung structure and the lung transcriptome. Parenteral administration of scrambled microRNA inhibitors (called antagomiRs) that are used to control in vivo microRNA neutralization studies, impacted lung volume, septal thickness, and the transcriptome of developing mouse lungs; with some effects dependent upon nucleotide sequence. Repeated intraperitoneal isotonic saline injections altered lung volume, with limited impact on the transcriptome. Parenteral administration of the tamoxifen solvent Miglyol accelerated mouse pup growth, and changed the abundance of 73 mRNA transcripts in the lung. Tamoxifen applied in Miglyol-in the absence of Cre recombinase-decreased pup growth, lung volume, and lung alveolarization and changed the abundance of 298 mRNA transcripts in the lung. These data demonstrate that widely used control interventions can directly impact lung alveolarization and the lung transcriptome in studies on lung development.

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“…Therefore, there is a possibility that the random coil conformation in the purified intermediates was maintained even after the hexane treatment, and that it deeply contributed to the attachment factors between the cells. Proline residues are generally abundant in the proteins formed with random coil conformation, such as collagen [ 49 ] and elastin [ 50 ], and proline is known to be deeply involved in protein–protein interactions. In view of the above, it is expected that the findings in this study will possibly be used, in the future, for matrix selection to create cell plastics with diverse properties.…”

Section: Discussionmentioning

confidence: 99%

Identification of Cell-Attachment Factors Derived from Green Algal Cells Disrupted by Sonication in Fabrication of Cell Plastics

et al. 2023

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Cell plastics which are composed of unicellular green algal cells have been proposed in previous studies. While unicellular green algae can be freely arranged using fabrication processes, a matrix is required to attach the cells together. To date, although the cell contents collected from Chlamydomonas reinhardtii show the possibility of attaching cells, but it is unclear which components can be considered attachment factors. Therefore, in this study, C. reinhardtii cells were disrupted with sonication, and the components were separated and purified with hexane. The cell plastics with only 0.5 wt% of intermediate showed similar mechanical properties to those with 17 wt% and 25 wt% of cell components that were untreated with hexane, meaning that the purified intermediates could function as matrices. The purified intermediate was composed of approximately 60 wt% of protein as the main component, and proteomic analysis was performed to survey the main proteins that remained after hexane treatment. The protein compositions of the cell content and purified intermediate were compared via proteomic analysis, revealing that the existing ratios of 532 proteins were increased in the purified intermediate rather than in the cell content. In particular, the outer structure of each of the 49 proteins—the intensity of which was increased by over 10 times—had characteristically random coil conformations, containing ratios of proline and alanine. The information could suggest a matrix of cell plastics, inspiring the possibility to endow the cell plastics with more properties and functions.

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Extracellular Assembly of the Elastin Cable Line Element in the Developing Lung

Cited by 8 publications

References 35 publications

Stochastic simulations of self-organized elastogenesis in the developing lung

Stochastic simulations of self-organized elastogenesis in the developing lung

Control Interventions Can Impact Alveolarization and the Transcriptome in Developing Mouse Lungs

Identification of Cell-Attachment Factors Derived from Green Algal Cells Disrupted by Sonication in Fabrication of Cell Plastics

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