Macromolecular gelatin properties affect fibrin microarchitecture and tumor spheroid behavior in fibrin-gelatin gels
Abstract
The biophysical properties of extracellular matrices (ECM) are known to regulate cell behavior, however decoupling cell behavior changes due to the relative contributions of material microstructure versus biomechanics or nutrient permeability remains challenging, especially within complex, multi-material matrices. We developed four gelatin-fibrin interpenetrating network (IPN) formulations which are identical in composition but possess variable gelatin molecular weight distributions, and display differences in microstructure, biomechanics, and diffusivity. In this work we interrogate the response of multicellular tumor spheroids to these IPN formulations and found that a high stiffness, gelatin-network dominated IPNs impeded remodeling and invasion of multicellular tumor spheroids; whereas relatively lower stiffness, fibrin-network dominated IPNs permitted protease-dependent remodeling and spheroid invasion. Cell proliferation correlated to nutrient diffusivity across tested IPN formulations. These findings demonstrate the complexity of ECM IPNs, relative to single polymer matrices, and highlight that cell response does not derive from a single aspect of the ECM, but rather from the interplay of multiple biomechanical properties. The methodology developed in this study represents a framework for future studies which aim to characterize cellular phenotypic responses to biophysical cues present within complex, multi-material matrices.
- Authors:
-
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1650420
- Alternate Identifier(s):
- OSTI ID: 1692052
- Report Number(s):
- LLNL-JRNL-800043
Journal ID: ISSN 0142-9612; 1003406
- Grant/Contract Number:
- AC52-07NA27344; LDRD-19-SI-003; LDRD-18-ERD-062
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biomaterials
- Additional Journal Information:
- Journal Volume: 250; Journal Issue: na; Journal ID: ISSN 0142-9612
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 36 MATERIALS SCIENCE; Hydrogel; Fibrin; Collagen; Extracellular matrices; Microstructure; Tumors
Citation Formats
Dubbin, Karen, Robertson, Claire, Hinckley, Aubree, Alvarado, Javier A., Gilmore, Sean F., Hynes, William F., Wheeler, Elizabeth K., and Moya, Monica L. Macromolecular gelatin properties affect fibrin microarchitecture and tumor spheroid behavior in fibrin-gelatin gels. United States: N. p., 2020.
Web. doi:10.1016/j.biomaterials.2020.120035.
Dubbin, Karen, Robertson, Claire, Hinckley, Aubree, Alvarado, Javier A., Gilmore, Sean F., Hynes, William F., Wheeler, Elizabeth K., & Moya, Monica L. Macromolecular gelatin properties affect fibrin microarchitecture and tumor spheroid behavior in fibrin-gelatin gels. United States. https://doi.org/10.1016/j.biomaterials.2020.120035
Dubbin, Karen, Robertson, Claire, Hinckley, Aubree, Alvarado, Javier A., Gilmore, Sean F., Hynes, William F., Wheeler, Elizabeth K., and Moya, Monica L. Tue .
"Macromolecular gelatin properties affect fibrin microarchitecture and tumor spheroid behavior in fibrin-gelatin gels". United States. https://doi.org/10.1016/j.biomaterials.2020.120035. https://www.osti.gov/servlets/purl/1650420.
@article{osti_1650420,
title = {Macromolecular gelatin properties affect fibrin microarchitecture and tumor spheroid behavior in fibrin-gelatin gels},
author = {Dubbin, Karen and Robertson, Claire and Hinckley, Aubree and Alvarado, Javier A. and Gilmore, Sean F. and Hynes, William F. and Wheeler, Elizabeth K. and Moya, Monica L.},
abstractNote = {The biophysical properties of extracellular matrices (ECM) are known to regulate cell behavior, however decoupling cell behavior changes due to the relative contributions of material microstructure versus biomechanics or nutrient permeability remains challenging, especially within complex, multi-material matrices. We developed four gelatin-fibrin interpenetrating network (IPN) formulations which are identical in composition but possess variable gelatin molecular weight distributions, and display differences in microstructure, biomechanics, and diffusivity. In this work we interrogate the response of multicellular tumor spheroids to these IPN formulations and found that a high stiffness, gelatin-network dominated IPNs impeded remodeling and invasion of multicellular tumor spheroids; whereas relatively lower stiffness, fibrin-network dominated IPNs permitted protease-dependent remodeling and spheroid invasion. Cell proliferation correlated to nutrient diffusivity across tested IPN formulations. These findings demonstrate the complexity of ECM IPNs, relative to single polymer matrices, and highlight that cell response does not derive from a single aspect of the ECM, but rather from the interplay of multiple biomechanical properties. The methodology developed in this study represents a framework for future studies which aim to characterize cellular phenotypic responses to biophysical cues present within complex, multi-material matrices.},
doi = {10.1016/j.biomaterials.2020.120035},
journal = {Biomaterials},
number = na,
volume = 250,
place = {United States},
year = {Tue Apr 14 00:00:00 EDT 2020},
month = {Tue Apr 14 00:00:00 EDT 2020}
}
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