Elucidating the role of matrix stiffness kid writes dating book
P., Pubill, S., Ribeiro, A., Leach, JB., “Hydrolytically degradable poly(ethylene glycol) hydrogel scaffolds as a cell delivery vehicle: characterization of PC12 cell response”, Biotechnology Progress, 2013, 29(5), 1255-1264 doi: 10.1021/btpr.1761 Zustiak, S. A., Nossal, R., “Effects of Multiple Scattering on Fluorescence Correlation Spectroscopy Measurements of Particles Moving within Optically Dense Media”, Journal of Biomedical Optics, 2012, 17(12), 125004-125004.
Tumor invasion and metastasis are strongly regulated by biophysical interactions between tumor cells and the extracellular matrix (ECM).
Specific mechanisms responsible for drug sensitivity in 3D versus 2D environments are investigated. B., “Protein-hydrogel interactions in tissue engineering: mechanisms and applications”, Tissue Engineering Reviews, 2012, 19(2): 160-171. P., Nossal, R., Sackett, D., “Hindered Diffusion in Polymeric Solutions Studied by Fluorescence Correlation Spectroscopy”, Biophysical Journal, 2011, 101, 255-264. P., Nossal, R., Sackett, D., “Development of a Polyacrylamide-Based Stiffness Assay for “High-Throughput” Drug Testing”, (Poster), Annual Biomedical Research Conference for Minority Students (ABRCMS), San Jose, CA, November 2012. P., Nossal, R., Sackett, D., “Development of a Polyacrylamide-Based Stiffness Assay for “High-Throughput” Drug Testing”, (Poster), National Institute of Health (NIH) Summer Research Program Poster Day, Bethesda, MD, August 2012. P., Nossal, R., “Effects of Scattering on Fluorescence Correlation Spectroscopy Measurements of Diffusion in Complex Media”, (Poster), Predictive Functional Tissue Models, Boston, MA, November, 2011. P., Nossal, R., Sackett, D., “Hindered Diffusion in Polymeric Solutions Studied by Fluorescence Correlation Spectroscopy”, (Poster), Biophysical Society Annual Meeting, Baltimore, MD, March 2011. P., Nossal, R., Sackett, D., “Development of Poly(ethylene Glycol)-Collagen 3D Scaffolds”, (Poster), 14th Annual Undergraduate Research Symposium in the Chemical and Biological Sciences at UMBC, Baltimore, MD, October 2011. P., “Development of Poly(ethylene Glycol)-Collagen 3D Scaffolds”, (Poster), National Institute of Health (NIH) Summer Research Program Poster Day, Bethesda, MD, August 2011. Zustiak conducted post-doctoral research for three years at the National Institutes of Health in Bethesda, MD, at the Laboratory of Integrative and Medical Biophysics under Ralph Nossal, utilizing spectroscopic techniques to study solute transport within hydrogel matrices.
Printed Archival Peer-Reviewed Journals Zustiak, S. P., Nossal, R., Sackett, D., “Multiwell stiffness assay for the study of cell responsiveness to cytotoxic drugs”, Biotechnology & Bioengineering, 2013, doi: 10.1002/bit.25097 Zustiak, S. Patents Kostov, Y, Petrova, S., Rao, G., “Optical Alcohol Sensor”, Provisional Application 60/720, 444.
The overall goal of this project is to gain a fundamental grasp of key cell-matrix interactions that affect the cells’ responsiveness to anticancer drugs, with emphasis on matrix stiffness, integrin adhesions and their synergistic effects, since these parameters profoundly affect cancer cell fate including the onset of malignancy.
The underlying hypothesis for this work is that matrix stiffness and integrin presentation are also important in drug resistance mechanisms (e.g.
by altering cytoskeletal tension or integrin expression).
Zustiak is also studying the role of matrix stiffness on cancer cell responsiveness to anticancer drugs.
In addition, she explores the synergistic effects of ligand density and substrate stiffness.
Zustiak’s primary research interests are in hydrogel biomaterials and tissue engineering, with emphasis on developing novel biomaterials as cell scaffolds and drug screening platforms, and elucidating matrix structure-property relationships as well as cell-matrix interactions.
Biomaterial-based models are crucial for bridging the gap between traditional tissue culture and animal models by providing a cell environment that closely mimics real tissue.
While ECM-based biophysical cues have been demonstrated to influence all of these steps (5), ECM stiffness has emerged as a particular parameter of interest given the observations that tumors are frequently more rigid than normal tissue and that exogenous tissue stiffening can facilitate tumorigenesis (6–13).
Much of the field’s understanding of matrix stiffness derives from studies in 2D culture, where polyacrylamide (PA) hydrogels conjugated with full-length ECM proteins have proven a versatile and robust paradigm for the independent control of ECM stiffness and biochemical ligand density (7–10, 13–15).