Doctoral Candidate
Materials Science & Engineering

BS, Massachusetts Institute of Technology, 2001 (materials science & engineering)

Nanofabrication 3024
2220 Campus Drive
Evanston, IL 60208-3108

(847) 467-4927 office
(847) 467-4929 lab
(847) 491-3010 facsimile

Email Krista

Krista L. Niece

The long-term goal of my research is adapting the peptide amphiphile nanofiber system for use in in situ biomedical applications, particularly nervous system repair. This project involves modification of the chemistry of the PA nanofiber scheme such that it is possible to cause gelation at physiological pH, as well as modification of the surface of the fiber so that it contains neurobiologically relevant signals. I am currently working on the biological characterization of the system I have developed, to determine cell response. I am also attempting to align the nanofibers, which may be useful in the guidance of cell processes.

I have developed a system that uses the headgroup charge instead of solution pH as a trigger for self-assembly. In this system, two PA's with oppositely charged headgroups are combined at neutral pH. Electrostatic attraction between the headgroups encourages self-assembly, and the same hydrophobic and structural considerations as before cause the self-assembly to take the form of nanofibers containing both peptide amphiphiles (Niece, et. al., JACS 2003).

Figure 1: AFM image of a branched PA bearing both the IKVAV and YIGSR epitopes.

To do this, I designed and synthesized a complementary pair of PA’s, oppositely charged in neutral solution, which would self-assemble together. This self-assembly scheme opens up the possibility of neutral-pH assembly as well as the potential to incorporate multiple biological signals into one fiber, more closely mimicking the natural extracellular environment. The PA molecules I designed for this purpose both contain laminin-1 sequences that interact with mammalian neurons: tyrosine-isoleucine-glycine-serine-arginine (YIGSR), which plays a role in cell adhesion, and isoleucine-lysine-valine-alanine-valine (IKVAV), which promotes neurite outgrowth. Both molecules can be induced to gel individually by pH adjustment, but are soluble at pH 7. When 1% solutions of the two PAs are mixed at pH 7, they spontaneously form a gel, and nanofibers similar to those seen in the pH assembled molecules can be seen using transmission electron microscopy. Mixing of the headgroups within a single fiber is evidenced by the NOESY spectrum of the mixed system.

Preliminary experiments in which neural progenitor cells are encapsulated in these gels show that the cells are viable after seven days. Continuing experiments will characterize the amount of process outgrowth and adhesion in the system as well as cell differentiation.

Attempts to align these fibers by various means are underway. Dielectrophoresis and magnetic alignment, as well as mechanical alignment, are being explored.

Publications

Silva, G. A.; Czeisler, C.; Niece, K. L.; Beniash, E.; Harrington, D. A.; Kessler, J. A.; Stupp, S. I. "Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers" Science 2004, 303, 1352-1355.

Niece, K. L.; Hartgerink, J. D.; Donners, J. J. J. M.; Stupp, S. I. "Self-Assembly Combining Two Bioactive Peptide-Amphiphile Molecules into Nanofibers by Electrostatic Attraction" J. Am. Chem. Soc. 2003, 125, 7146-7147.