Gelatin-Based Matrices as a Tunable Platform to Study in Vitro and in Vivo 3D Cell Invasion

Mathew Peter, Archana Singh, Kumaravel Mohankumar, Rajeev Jeenger, Puja Arun Joge, Madhumanjiri Mukulesh Gatne, Prakriti Tayalia

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Hydrogels have been used as synthetic mimics of 3D extracellular matrices (ECM) and their physical properties like stiffness, degradability, and porosity have been known to influence the behavior of encapsulated cells. However, to understand the role of individual properties, the influence of biophysical cues should be decoupled from biochemical ones. In this study, we have used hydrogels as a tunable model matrix to develop a 3D cell culture platform for studying cell invasion. Inert polyethylene (glycol) diacrylate (PEGDA) and cell adhesive gelatin methacryloyl (GELMA) were blended in varying compositions, followed by UV-mediated photo polymerization to obtain hydrogels with varying stiffness, degradation, and cell adhesive properties. We developed two hydrogel matrix systems, namely, PEGDA-GELMA (containing a larger proportion of PEGDA) and GELMA-PEGDA (containing predominantly GELMA), and characterized them for differences in pore size, swelling ratio, storage modulus, degradability, and biocompatibility of the matrix. Both hydrogel systems had similar pore dimensions and swelling behavior, but PEGDA-GELMA was found to be stiffer and nondegradable, while GELMA-PEGDA was softer and degradable. Accordingly, MDA-MB-231 breast cancer cells encapsulated in these matrices showed a spheroidal morphology in PEGDA-GELMA hydrogels and were more spindle-shaped in GELMA-PEGDA hydrogels, confirming that size and extent of spreading of cells were influenced by the type of these hydrogels. The softer GELMA-PEGDA matrices readily allowed invasion of MDA-MB-231 cells in 3D and showed differences in epithelial-mesenchymal transition (EMT) gene expression of these cells. We further demonstrated the invasion and sprouting of endothelial cells using a chick aortic arch assay, exhibiting the utility of softer matrices to study 3D cell invasion for multiple applications. We also implanted these matrices in mice and showed that soft gelatin-based hydrogels allow cell infiltration in vivo. Results from our study highlight the tunability of this matrix system and the role of matrix constitution in influencing cell invasion in a 3D microenvironment.

Original languageEnglish
Pages (from-to)916-929
Number of pages14
JournalACS Applied Bio Materials
Volume2
Issue number2
DOIs
Publication statusPublished - 18-02-2019
Externally publishedYes

Fingerprint

Gelatin
Hydrogels
Polyethylene glycols
Hydrogel
Swelling
Adhesives
Cells
Stiffness
In Vitro Techniques
Photopolymerization
Endothelial cells
Arches
Biocompatibility
Cell culture
Infiltration
Epithelial-Mesenchymal Transition
Gene expression
Porosity
Constitution and Bylaws
Pore size

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical

Cite this

Peter, M., Singh, A., Mohankumar, K., Jeenger, R., Joge, P. A., Gatne, M. M., & Tayalia, P. (2019). Gelatin-Based Matrices as a Tunable Platform to Study in Vitro and in Vivo 3D Cell Invasion. ACS Applied Bio Materials, 2(2), 916-929. https://doi.org/10.1021/acsabm.8b00767
Peter, Mathew ; Singh, Archana ; Mohankumar, Kumaravel ; Jeenger, Rajeev ; Joge, Puja Arun ; Gatne, Madhumanjiri Mukulesh ; Tayalia, Prakriti. / Gelatin-Based Matrices as a Tunable Platform to Study in Vitro and in Vivo 3D Cell Invasion. In: ACS Applied Bio Materials. 2019 ; Vol. 2, No. 2. pp. 916-929.
@article{bdc5f829eb734c52a54cc949e78a2682,
title = "Gelatin-Based Matrices as a Tunable Platform to Study in Vitro and in Vivo 3D Cell Invasion",
abstract = "Hydrogels have been used as synthetic mimics of 3D extracellular matrices (ECM) and their physical properties like stiffness, degradability, and porosity have been known to influence the behavior of encapsulated cells. However, to understand the role of individual properties, the influence of biophysical cues should be decoupled from biochemical ones. In this study, we have used hydrogels as a tunable model matrix to develop a 3D cell culture platform for studying cell invasion. Inert polyethylene (glycol) diacrylate (PEGDA) and cell adhesive gelatin methacryloyl (GELMA) were blended in varying compositions, followed by UV-mediated photo polymerization to obtain hydrogels with varying stiffness, degradation, and cell adhesive properties. We developed two hydrogel matrix systems, namely, PEGDA-GELMA (containing a larger proportion of PEGDA) and GELMA-PEGDA (containing predominantly GELMA), and characterized them for differences in pore size, swelling ratio, storage modulus, degradability, and biocompatibility of the matrix. Both hydrogel systems had similar pore dimensions and swelling behavior, but PEGDA-GELMA was found to be stiffer and nondegradable, while GELMA-PEGDA was softer and degradable. Accordingly, MDA-MB-231 breast cancer cells encapsulated in these matrices showed a spheroidal morphology in PEGDA-GELMA hydrogels and were more spindle-shaped in GELMA-PEGDA hydrogels, confirming that size and extent of spreading of cells were influenced by the type of these hydrogels. The softer GELMA-PEGDA matrices readily allowed invasion of MDA-MB-231 cells in 3D and showed differences in epithelial-mesenchymal transition (EMT) gene expression of these cells. We further demonstrated the invasion and sprouting of endothelial cells using a chick aortic arch assay, exhibiting the utility of softer matrices to study 3D cell invasion for multiple applications. We also implanted these matrices in mice and showed that soft gelatin-based hydrogels allow cell infiltration in vivo. Results from our study highlight the tunability of this matrix system and the role of matrix constitution in influencing cell invasion in a 3D microenvironment.",
author = "Mathew Peter and Archana Singh and Kumaravel Mohankumar and Rajeev Jeenger and Joge, {Puja Arun} and Gatne, {Madhumanjiri Mukulesh} and Prakriti Tayalia",
year = "2019",
month = "2",
day = "18",
doi = "10.1021/acsabm.8b00767",
language = "English",
volume = "2",
pages = "916--929",
journal = "ACS Applied Bio Materials",
issn = "2576-6422",
publisher = "American Chemical Society",
number = "2",

}

Peter, M, Singh, A, Mohankumar, K, Jeenger, R, Joge, PA, Gatne, MM & Tayalia, P 2019, 'Gelatin-Based Matrices as a Tunable Platform to Study in Vitro and in Vivo 3D Cell Invasion', ACS Applied Bio Materials, vol. 2, no. 2, pp. 916-929. https://doi.org/10.1021/acsabm.8b00767

Gelatin-Based Matrices as a Tunable Platform to Study in Vitro and in Vivo 3D Cell Invasion. / Peter, Mathew; Singh, Archana; Mohankumar, Kumaravel; Jeenger, Rajeev; Joge, Puja Arun; Gatne, Madhumanjiri Mukulesh; Tayalia, Prakriti.

In: ACS Applied Bio Materials, Vol. 2, No. 2, 18.02.2019, p. 916-929.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gelatin-Based Matrices as a Tunable Platform to Study in Vitro and in Vivo 3D Cell Invasion

AU - Peter, Mathew

AU - Singh, Archana

AU - Mohankumar, Kumaravel

AU - Jeenger, Rajeev

AU - Joge, Puja Arun

AU - Gatne, Madhumanjiri Mukulesh

AU - Tayalia, Prakriti

PY - 2019/2/18

Y1 - 2019/2/18

N2 - Hydrogels have been used as synthetic mimics of 3D extracellular matrices (ECM) and their physical properties like stiffness, degradability, and porosity have been known to influence the behavior of encapsulated cells. However, to understand the role of individual properties, the influence of biophysical cues should be decoupled from biochemical ones. In this study, we have used hydrogels as a tunable model matrix to develop a 3D cell culture platform for studying cell invasion. Inert polyethylene (glycol) diacrylate (PEGDA) and cell adhesive gelatin methacryloyl (GELMA) were blended in varying compositions, followed by UV-mediated photo polymerization to obtain hydrogels with varying stiffness, degradation, and cell adhesive properties. We developed two hydrogel matrix systems, namely, PEGDA-GELMA (containing a larger proportion of PEGDA) and GELMA-PEGDA (containing predominantly GELMA), and characterized them for differences in pore size, swelling ratio, storage modulus, degradability, and biocompatibility of the matrix. Both hydrogel systems had similar pore dimensions and swelling behavior, but PEGDA-GELMA was found to be stiffer and nondegradable, while GELMA-PEGDA was softer and degradable. Accordingly, MDA-MB-231 breast cancer cells encapsulated in these matrices showed a spheroidal morphology in PEGDA-GELMA hydrogels and were more spindle-shaped in GELMA-PEGDA hydrogels, confirming that size and extent of spreading of cells were influenced by the type of these hydrogels. The softer GELMA-PEGDA matrices readily allowed invasion of MDA-MB-231 cells in 3D and showed differences in epithelial-mesenchymal transition (EMT) gene expression of these cells. We further demonstrated the invasion and sprouting of endothelial cells using a chick aortic arch assay, exhibiting the utility of softer matrices to study 3D cell invasion for multiple applications. We also implanted these matrices in mice and showed that soft gelatin-based hydrogels allow cell infiltration in vivo. Results from our study highlight the tunability of this matrix system and the role of matrix constitution in influencing cell invasion in a 3D microenvironment.

AB - Hydrogels have been used as synthetic mimics of 3D extracellular matrices (ECM) and their physical properties like stiffness, degradability, and porosity have been known to influence the behavior of encapsulated cells. However, to understand the role of individual properties, the influence of biophysical cues should be decoupled from biochemical ones. In this study, we have used hydrogels as a tunable model matrix to develop a 3D cell culture platform for studying cell invasion. Inert polyethylene (glycol) diacrylate (PEGDA) and cell adhesive gelatin methacryloyl (GELMA) were blended in varying compositions, followed by UV-mediated photo polymerization to obtain hydrogels with varying stiffness, degradation, and cell adhesive properties. We developed two hydrogel matrix systems, namely, PEGDA-GELMA (containing a larger proportion of PEGDA) and GELMA-PEGDA (containing predominantly GELMA), and characterized them for differences in pore size, swelling ratio, storage modulus, degradability, and biocompatibility of the matrix. Both hydrogel systems had similar pore dimensions and swelling behavior, but PEGDA-GELMA was found to be stiffer and nondegradable, while GELMA-PEGDA was softer and degradable. Accordingly, MDA-MB-231 breast cancer cells encapsulated in these matrices showed a spheroidal morphology in PEGDA-GELMA hydrogels and were more spindle-shaped in GELMA-PEGDA hydrogels, confirming that size and extent of spreading of cells were influenced by the type of these hydrogels. The softer GELMA-PEGDA matrices readily allowed invasion of MDA-MB-231 cells in 3D and showed differences in epithelial-mesenchymal transition (EMT) gene expression of these cells. We further demonstrated the invasion and sprouting of endothelial cells using a chick aortic arch assay, exhibiting the utility of softer matrices to study 3D cell invasion for multiple applications. We also implanted these matrices in mice and showed that soft gelatin-based hydrogels allow cell infiltration in vivo. Results from our study highlight the tunability of this matrix system and the role of matrix constitution in influencing cell invasion in a 3D microenvironment.

UR - http://www.scopus.com/inward/record.url?scp=85071726290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071726290&partnerID=8YFLogxK

U2 - 10.1021/acsabm.8b00767

DO - 10.1021/acsabm.8b00767

M3 - Article

VL - 2

SP - 916

EP - 929

JO - ACS Applied Bio Materials

JF - ACS Applied Bio Materials

SN - 2576-6422

IS - 2

ER -