Bulletin of the American Physical Society
Annual Meeting of the APS Four Corners Section
Volume 60, Number 11
Friday–Saturday, October 16–17, 2015; Tempe, Arizona
Session D10: Biophysics III: Interfaces, Biotechnology and Medical Physics |
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Chair: Sefika Banu Ozkan, Arizona State University Room: MU228 |
Friday, October 16, 2015 1:50PM - 2:14PM |
D10.00001: Assessing how membrane curvature alters protein recruitment Invited Speaker: Carrie Moon Cellular membranes exhibit a diversity of curvatures that serve to recruit or sort proteins to certain regions within the cell. Due to the complexity of the process that occurs at sites of curvature in cells, it is difficult to determine what molecular interactions are essential to the sorting process. In order to identify individual interactions, our lab has created a biophysical assay that mimics a cellular membrane with areas of curvature. The design of this in vitro assay allows for specific and separate adjustments of the lipid composition and the membrane curvature, which is provided by a nanopatterned substrate under a supported lipid bilayer. In our work, fluorescent, polystyrene nanoparticles were placed on a glass surface to form the nanopatterned substrate, upon which liposomes were deposited to create a supported lipid bilayer, and then proteins of interest were allowed to interact with the lipids and/or curvature. Both laser scanning confocal and total internal reflection fluorescence microscopy were used to characterize curvature binding events. Colocalization analysis of the images using an object-oriented method provides a precise evaluation of the areas around each fluorescent nanoparticle to determine whether or not a protein is recruited to curved membranes. The applications of this assay are broad due to its ability to evaluate the interactions of either lipids or proteins with curvature. Using this assay, we have evaluated if C-Reactive Protein (CRP) preferentially binds to curved membranes. CRP is known to bind to small mimics of LDL particles that contain highly curved membranes, but it is not clear whether the conformational state affects binding. CRP has a native, anti-inflammatory, pentameric (pCRP) form and a pro-inflammatory, modified (mCRP) form. The mechanism for converting pCRP to mCRP remains elusive. Our results show that the conformational state of mCRP binds preferentially to sites of curvature and this binding is enhanced with the presence of specific lipids. [Preview Abstract] |
Friday, October 16, 2015 2:14PM - 2:26PM |
D10.00002: High-frequency ultrasound for evaluating margins during breast conservation surgery: Results from a 17-patient pilot study Robyn Omer Obtaining negative (cancer-free) margins in breast conservation surgery (BCS) is essential for ensuring all of the cancer has been removed from the excision site. Several noninvasive cancer detection methods are therefore being investigated for the intraoperative evaluation of margin status. This study investigated high-frequency (HF) ultrasound (20-80 MHz) as an intraoperative margin evaluation technique during BCS. In a 17-patient pilot study at the Huntsman Cancer Institute, Salt Lake City, Utah, through-transmission and pulse-echo measurements were acquired from 53 positions on specimens including margins, tumors, lymph nodes, and fibroadenomas. Measurements were acquired with the use of two 50-MHz transducers, a HF square-wave pulser/receiver, a 500-MHz digital oscilloscope, and a notebook PC. Parameters calculated from the data included peak density (the number of peaks and valleys across the ultrasonic spectrum), attenuation, and the slope of the second Fourier transform. Statistical analysis of the data revealed that a multivariate analysis combining peak density and attenuation provided the highest accuracy and sensitivity for differentiating malignant from nonmalignant tissue. The multivariate analysis showed 81.1% accuracy, 76.9% sensitivity, and 85.2% specificity. [Preview Abstract] |
Friday, October 16, 2015 2:26PM - 2:38PM |
D10.00003: Magnetic nanodrug delivery through the mucus layer of air-liquid interface cultured primary normal human tracheobronchial epithelial cells. Kathrin Spendier, Evangelos Economou, Simon Marinelli, Zbigniew Celinski, Hong Chu In several prominent human lung diseases, such as asthma, patients produce a thickened mucosal fluid, irritating and inflaming the underlying tissue that progresses the condition. Many current drug therapies prove ineffective due to the inability to penetrate this thickened mucosal layer. In this study, superparamagnetic Fe$_{\mathrm{3}}$O$_{\mathrm{4}}$ and highly anisotropic BaFe$_{\mathrm{12}}$O$_{\mathrm{19}}$ nanoparticles were surface-engineered for the purpose of transporting anti-mucin medicine through the mucus layer of air-liquid interface cultured primary normal human tracheobronchial epithelial (NHTE) cells via magnetic field gradient. Using wet planetary ball milling, surfactant-coated BaFe$_{\mathrm{12}}$O$_{\mathrm{19}}$ nanoparticles (BaNPs) of 60 nm in diameter were prepared in water. BaNPs and conventional 30 nm surfactant-coated Fe$_{\mathrm{3}}$O$_{\mathrm{4}}$ nanoparticles (FeNPs) were then encased in a polymer (PLGA) loaded with dexamethasone (Dex) and tagged for imaging. Both PLGA-Dex coated BaNPs and FeNPs were added on top of an approximately 100 micrometer thick mucus layer of air-liquid interface cultured NHTE cells. Within 30 minutes, PLGA-Dex coated FeNPs and BaNPs were pulled successfully through the mucus layer by a permanent neodymium magnet for the first time. The penetration time of the nanomedicine was monitored using confocal microscopy. [Preview Abstract] |
Friday, October 16, 2015 2:38PM - 2:50PM |
D10.00004: High-Frequency Ultrasound for Assessing Breast Cancer Surgical Margins: Evaluating the Effect of Breast Density using Histology Mimicking Phantoms Zachary Coffman, Nicole Cowan, Robyn Omer, Timothy Doyle Breast density is typically determined using mammography, and describes the proportion of connective tissue versus fat tissue in the breast. Women with higher breast density are four to five times more likely to develop breast cancer than women with lower breast densities. Clinical studies performed in collaboration between Utah Valley University and the Huntsman Cancer Institute show that high-frequency (HF) ultrasound (20-80 MHz), and the parameters peak density and attenuation, are sensitive to breast tissue pathology. These studies also showed that breast density had no effect on peak density while attenuation increases two times from entirely fat to extremely dense. The objective of this study was to determine the effect of breast density on HF ultrasound wave propagation using phantoms that mimic breast tissue histology. Phantoms were created from distilled water, agarose powder, 10X TBE stock solution, and polyethylene microspheres. Pitch-catch measurements were acquired using 50-MHz transducers, a HF pulser-receiver, and a 1-GHz digital oscilloscope. Peak density showed no significant change with increasing breast density, whereas attenuation showed sensitivity to the total weight percent of scatterers. The phantom results confirm the results seen in clinical studies. [Preview Abstract] |
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