Traditional 2-D cell cultures have many limitations because they do not truly mimic the natural environment. In order to fully understand the in vivo 3-D environment, it is crucial to develop a biomimetic 3-D culture system. Recently progress toward 3-D tissue cell cultures has been gradually made by addressing many critical issues including the microenvironment, gradient diffusion and apoptosis. Here we report a D-form self-assembly peptide system that provides insight into the relationships between nanofiber scaffolds and cell behaviors in 3-D cell cultures. We observed the peptide secondary structures response to ions and confirmed that their participation increases mechanical force rapidly. We also showed the enzymes attachment to nanofibers, investigated scaffolds to form 3-D microenvironment and described a modified protocol for 3-D cell culture D-form self-assembly peptide. Using this protocol, we showed cell behavior in the D-form peptide with high cell viability and low-level cell apoptosis for weeks. Furthermore, we proposed a plausible model for chiral self-assembly peptides in 3-D culture. Our research may further stimulate others to design novel biological materials at single chiral amino acid level, and may broaden the applications of designer D-form self-assembling peptides in clinical and medical nanobiotechnology.
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