Characterizing the Mechanical Properties of the Tumor Extracellular Matrix with a DNA Origami Sensor
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Date
2018-05
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The Ohio State University
Abstract
Tumor growth and metastasis are believed to be promoted by alterations to the mechanical properties of the extracellular matrix (ECM). These mechanical alterations in tumors are also highly dynamic, but our understanding of the exact causes and consequences of tumor ECM remodeling is constrained by the current methodologies used to measure them. Therefore, the goal of this study was to better understand stability and matrix properties by developing a new sensor capable of detecting for alterations in the mechanical properties of the ECM with improved temporal and spatial resolution compared to current methodologies. To achieve this goal, we used the NanoDyn, a DNA origami nanostructure, which has been previously used to measure the effects of macromolecular crowding on the rheological properties of polyethylene glycol solutions. Our study aimed to adapt the NanoDyn for measuring stability and dynamic changes of the mechanical properties of the tumor ECM. The NanoDyn detection scheme consists of a double barrel structure which can be either in an open or closed state depending on its surroundings. The state of the device is found by fluorescence resonance energy transfer (FRET) due to the changing proximity of two fluorophores. By measuring stability and overlap concentration of well-characterized polymer solutions, the NanoDyn was initially characterized. Subsequently, stability testing for the NanoDyn in collagen and hyaluronan, which are two of the main constituents of tumor ECM, were conducted using transmission electron microscopy (TEM) and gel electrophoresis. Results from the overlap concentration measurements showed that the NanoDyn measurements coincide with accepted literature. Additionally, the NanoDyn has been found to be stable in collagen for two weeks by changing the solution composition from magnesium chloride to sodium chloride. Therefore, the NanoDyn structure has the capability of measuring biological components of the microenvironment due to early successes in stability and measurement. In future investigation, the NanoDyn in collagen and hyaluronan solutions will be analyzed using FRET to determine how these biological components impact the state of the NanoDyn. These findings would provide a better understanding of the tumor promoting properties of two of the main components of the ECM.
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Keywords
tumor development, extracellular matrix, DNA origami, matrix remodeling