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The Stiffness of Three-dimensional Ionic Self-assembling Peptide Gels Affects the Extent of Capillary-like Network Formation

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Abstract

Improving our ability to control capillary morphogenesis has implications for not only better understanding of basic biology, but also for applications in tissue engineering and in vitro testing. Numerous biomaterials have been investigated as cellular supports for these applications and the biophysical environment biomaterials provide to cells has been increasingly recognized as an important factor in directing cell function. Here, the ability of ionic self-assembling peptide gels to support capillary morphogenesis and the effect of their mechanical properties is investigated. When placed in a physiological salt solution, these oligopeptides spontaneously self-assemble into gels with an extracellular matrix (ECM)-like microarchitecture. To evaluate the ability of three-dimensional (3D) self-assembled peptide gels to support capillary-like network formation, human umbilical vein endothelial cells (HUVECs) were embedded within RAD16-I ((RADA)4) or RAD16-II ((RARADADA)2) peptide gels with various stiffness values. As peptide stiffness is decreased cells show increased elongation and are increasingly able to contract gels. The observation that capillary morphogenesis is favored in more malleable substrates is consistent with previous reports using natural biomaterials. The structural properties of peptide gels and their ability to support capillary morphogenesis in vitro make them promising biomaterials to investigate for numerous biomedical applications.

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Acknowledgements

The authors thank the generosity of Gareth McKinley for use of his rheometer, 3DM for the generous gift of RAD16-I (BD PuraMatrix), and Keith Gooch, Lisa Spirio, and Carlos Semino for insightful discussions. The authors also gratefully acknowledge funding from the National Institutes of Health (#R01-EB003805 to RDK and Ruth L. Kirschstein National Research Service Award to ALS), Draper Laboratory University IR&D Grant DL-H-550151, and the National Science Foundation Major Research Instrumentation Program (#BES-0619373 to ALS).

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Sieminski, A.L., Was, A.S., Kim, G. et al. The Stiffness of Three-dimensional Ionic Self-assembling Peptide Gels Affects the Extent of Capillary-like Network Formation. Cell Biochem Biophys 49, 73–83 (2007). https://doi.org/10.1007/s12013-007-0046-1

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  • DOI: https://doi.org/10.1007/s12013-007-0046-1

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