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Pilot Projects

Joel Collier, Ph.D. (University of Chicago), is the project leader. Co-investigators involved in the project are: Maciej Lesniak, M.D. (University of Chicago); David Eddington, Ph.D. (University of Illinois Chicago); Milan Mrksich, Ph.D.; Chad A. Mirkin, Ph.D.; Hidayatullah G. Munshi, M.D.; Samuel Stupp, Ph.D.; and Steven T. Rosen, M.D.

A broad challenge in cancer biology is the development of cell culture models that are physiologically relevant in that the resident cells display the complex behaviors that underlie disease. Planar cultures performed on plastic dishes are often insufficient to capture relevant cell behaviors, and the common Matrigel three-dimensional matrix has been important to cancer biology, notwithstanding the variable properties of and incompletely-defined composition of this natural matrix.

This project is pursuing molecular approaches to developing two classes of defined matrices. One is based on nanopatterned substrates and is significant because the patterns can be used to constrain the sizes of focal adhesions—making them more relevant to what is observed in cells within tissue—and provides a reproducible microenvironment to cells, thereby removing one source of heterogeneous behavior.

The second approach is based on three-dimensional matrices that are self-assembled from peptide amphiphiles and is significant for the use of a completely defined composition that also permits wide flexibility in incorporating peptide and protein motifs. Both designs emphasize the control of material properties at the nanoscale—either in the dimensions of patterned extracellular matrix or the sizes of the fibrils in the three-dimensional matrices—and therefore mimic the physical features of protein matrix.

The project emphasizes the development and characterization of the matrices, but is significant because it includes investigators with expertise in the biology and medicine of brain and pancreatic cancer, providing a real test-bed for evaluating the matrices. The broad goal of the project is to develop culture systems that are unmatched for providing cells with a microenvironment that supports complex biological functions. This work, if successful, will therefore be important in basic research laboratories—but also in programs to use cell-based assays in high-throughput screens and possibly as materials that provide for regeneration of tissue in the treatment of cancer.

This project team is collaborating with NanoInk, the commercial developer and provider of instruments for Dip Pen Nanolithography, developed in the Mirkin Group. NanoInk has an internal program to develop applications of nanopatterned substrates for the life sciences and for that reason is interested in providing commercial substrates that enable a broad dissemination of the proposed substrates.