Macromolecular crowding tunes 3D collagen architecture and cell morphogenesis

Ranamukhaarachchi, Sural; Modi, Rishi N; Han, Aijie; Velez, Daniel Ortiz; Kumar, Aditya; Engler, Adam J.; Fraley, Stephanie I.

doi:10.1039/c8bm01188e

Cited by 47 publications

(47 citation statements)

References 82 publications

(101 reference statements)

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“…[ 274 ] The crowding effect produces tighter fibril networks and decreases susceptibility of proteinase‐mediated degradation, without significantly altering matrix stiffness. [ 275 ] A novel bioprinting strategy has been implemented to tune the degree of MMC within each printed region to create 3D bioprinted hierarchical porous collagen‐based constructs [ 268 ] ( Figure 7 ). The use of macromolecules manipulates the collagen fibrillogenesis process by exerting an excluded volume effect on the surrounding collagen molecules; an increasing macromolecule concentration results in the formation of larger pores and increased porosity within the 3D collagen matrices.…”

Section: Potentialsmentioning

confidence: 99%

Bioprinting of Collagen: Considerations, Potentials, and Applications

Lee

Suen

Ng³

et al. 2020

Macromolecular Bioscience

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Collagen is the most abundant extracellular matrix protein that is widely used in tissue engineering (TE). There is little research done on printing pure collagen. To understand the bottlenecks in printing pure collagen, it is imperative to understand collagen from a bottom‐up approach. Here it is aimed to provide a comprehensive overview of collagen printing, where collagen assembly in vivo and the various sources of collagen available for TE application are first understood. Next, the current printing technologies and strategy for printing collagen‐based materials are highlighted. Considerations and key challenges faced in collagen printing are identified. Finally, the key research areas that would enhance the functionality of printed collagen are presented.

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Section: Potentialsmentioning

confidence: 99%

Bioprinting of Collagen: Considerations, Potentials, and Applications

Lee

Suen

Ng³

et al. 2020

Macromolecular Bioscience

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“…Gels were polymerized at 37°C in a humidified incubator. To modify the structure of the collagen fibers to obtain LDSF gels we used a technique previously reported by our group [11]. Briefly, Polyethylene glycol (PEG, MW = 8000, Sigma, St. Louis, MO) was solubilized in phosphate-buffered solution (PBS) and filter sterilized.…”

Section: D Culture In Collagen I Matrixmentioning

confidence: 99%

“…To study the influence of matrix architecture on cancer cell migration, we used a previously developed method to tuned collagen fibril organization independently of altering density and stiffness by molecular crowding with polyethylene glycol (PEG) during polymerization and cell embedding [9,11]. PEG, an inert crowding agent, was subsequently washed out of the polymerized matrix.…”

Section: D Collagen Architecture Is Tuned By Molecular Crowdingmentioning

confidence: 99%

3D collagen architecture regulates cell adhesion through degradability, thereby controlling metabolic and oxidative stress

Velez

Ranamukhaarachchi

Kumar

et al. 2019

Integrative Biology

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The collagen-rich tumor microenvironment plays a critical role in directing the migration behavior of cancer cells. 3D collagen architectures with small pores have been shown to confine cells and induce aggressive collective migration, irrespective of matrix stiffness and density. However, it remains unclear how cells sense collagen architecture and transduce this information to initiate collective migration. Here, we tune collagen architecture and analyze its effect on four core cell-ECM interactions: cytoskeletal polymerization, adhesion, contractility, and matrix degradation. From this comprehensive analysis, we deduce that matrix architecture initially modulates cancer cell adhesion strength, and that this results from architecture-induced changes to matrix degradability. That is, architectures with smaller pores are less degradable, and degradability is required for cancer cell adhesion to 3D fibrilar collagen. The biochemical consequences of this 3D low-attachment state are similar to those induced by suspension culture, including metabolic and oxidative stress. One distinction from suspension culture is the induction of collagen catabolism that occurs in 3D low-attachment conditions. Cells also upregulate Snail1 and Notch signaling in response to 3D low-attachment, which suggests a mechanism for the emergence of collective behaviors.

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“…Another interesting observation is, that the ECM produced by adult fibroblasts under MMC conditions is able to propagate human embryonic stem cells, even outperforming Matrigel ( 19 ). With respect to natural biomaterials, it was found that MMC not only enhances the polymerization rate of collagen type I, but also tunes fiber diameter and organization, a fact that can be explored for optimizing the properties of soft collagen hydrogels ( 20 – 23 ) or collagen films (planar constructs) ( 24 , 25 ). Lastly, MMC has also been used for improving hydrogels derived from decellularized matrices ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited

et al. 2021

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An unsolved therapeutic problem in fibrosis is the overproduction of collagen. In order to screen the effect of anti-fibrotic drugs on collagen deposition, the Scar-in-a-Jar approach has been introduced about a decade ago. With macromolecular crowding a rapid deposition of collagen is seen, resulting in a substantial decrease in culture time, but the system has never been tested in an adequate way. We therefore have compared six different macromolecular crowders [Ficoll PM 70 (Fc70), Ficoll PM 400 (Fc400), a mixture of Ficoll 70 and 400 (Fc70/400), polyvinylpyrrolidone 40 (PVP40), polyvinylpyrrolidone 360 (PVP360), neutral dextran 670 (ND670), dextran sulfate 500 (DxS500), and carrageenan (CR)] under profibrotic conditions (addition of TGFβ1) with primary human adult dermal fibroblasts in the presence of 0.5 and 10% FBS. We found that (1) collagen deposition and myofibroblast formation was superior with 0.5% FBS, (2) DxS500 and CR results in an aberrant collagen deposition pattern, (3) ND670 does not increase collagen deposition, and (4) CR, DxS500, and Fc40/700 affected important phenotypical properties of the cells when cultured under pro-fibrotic conditions, whereas PVP40 and PVP360 did less or not. Because of viscosity problems with PVP360, we conclude that PVP40 is the most optimal crowder for the screening of anti-fibrotic drugs. Finally, the effect of various concentrations of Imatinib, Galunisertib, Omipalisib or Nintedanib on collagen deposition and myofibroblast formation was tested with PVP40 as the crowder.

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Macromolecular crowding tunes 3D collagen architecture and cell morphogenesis

Abstract: Macromolecular crowding of collagen I during polymerization produces short, degradation-resistant fibrils that induce collective morphogenesis of breast cancer cells.

Cited by 47 publications

References 82 publications

Bioprinting of Collagen: Considerations, Potentials, and Applications

Bioprinting of Collagen: Considerations, Potentials, and Applications

3D collagen architecture regulates cell adhesion through degradability, thereby controlling metabolic and oxidative stress

Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited

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