Self-Assembling Peptide Nanofiber Constructs as Defined 3D Cell Culture Matrices

Abstract

The field of prostate cancer research suffers from a lack of suitable in vitro culture models, and primary human prostate cancer cells are notoriously difficult to culture reliably, especially in 3D. As an alternative to the ill-defined, costly, and highly variable Matrigel, self-assembled peptides have been developed, though they too suffer from the major drawback of low cell survival during encapsulation process, mostly due to its acidic environment. Here we designed a novel peptide, bQ13; it undergoes gelation at a comparatively neutral pH range. In this project, I will demonstrate its excellent cytocompatibility and ability to provide a chemically defined and controllable matrix for drug screening. My data suggest that bQ13 hydrogels indeed greatly enhanced the cell survival rate during the encapsulation process in comparison to PuraMatrix and Q11, previously developed self-assembling peptides. The increased cytocompatibility of bQ13 ultimately enabled to the formation of prostate cancer cell spheroids in long-term 3D culture. Drug screening results showed that bQ13 hydrogels also significantly shielded the spheroids from enzalutamide compared to the other hydrogel samples, indicating it is a system that more closely mimics the in vivo environment compared to Matrigel and other self-assembling peptides.