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MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility

https://doi.org/10.1038/s41598-019-56983-x

Calhoun, Mark A. ; Cui, Yixiao ; Elliott, Eileen E. ; Mo, Xiaokui ; Otero, Jose J. ; Winter, Jessica O. ( January 2020 , Scientific Reports)

Abstract
Glioblastoma (GBM) is an astrocytic brain tumor with median survival times of <15 months, primarily as a result of high infiltrative potential and development of resistance to therapy (i.e., surgical resection, chemoradiotherapy). A prominent feature of the GBM microenvironment is compressive solid stress (CSS) caused by uninhibited tumor growth within the confined skull. Here, we utilized a mechanical compression model to apply CSS (<115 Pa) to well-characterized LN229 and U251 GBM cell lines and measured their motility, morphology, and transcriptomic response. Whereas both cell lines displayed a peak in migration at 23 Pa, cells displayed differential response to CSS with either minimal (i.e., U251) or large changes in motility (i.e., LN229). Increased migration of LN229 cells was also correlated to increased cell elongation. These changes were tied to epigenetic signaling associated with increased migration and decreases in proliferation predicted via Ingenuity® Pathway Analysis (IPA), characteristics associated with tumor aggressiveness. miRNA-mRNA interaction analysis revealed strong influence of the miR548 family (i.e., mir-548aj, mir-548az, mir-548t) on differential signaling induced by CSS, suggesting potential targets for pharmaceutical intervention that may improve patient outcomes.

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Magnetic Quantum Dots Steer and Detach Microtubules From Kinesin‐Coated Surfaces

https://doi.org/10.1002/biot.201700402

Mahajan, Kalpesh D. ; Cui, Yixiao ; Dorcéna, C. Jenny ; Bouxsien, Nathan F. ; Bachand, George D. ; Chalmers, Jeffrey J. ; Winter, Jessica O. ( October 2017 , Biotechnology Journal)

The microtubule (MT)‐kinesin system has been extensively studied because of its role in cellular processes, as well as its potential use for controllably transporting objects at the nanoscale. Thus, there is substantial interest in methods to evaluate MT properties, including bending radius and the binding energy of kinesin motor proteins to MT tracks. Current methods to identify these properties include optical tweezers, microfluidic devices, and magnetic fields. Here, the use of magnetic quantum dots (i.e., MagDots) is evaluated as a method to study MT‐kinesin interactions via applied magnetic forces. Magnetic fields are generated using a magnetic needle whose field gradient is quantified by finite element modeling (FEM). Magnetic force is applied to MagDot‐labeled MTs and demonstrated sufficient to steer and detach MTs from kinesin‐coated surfaces. Taking advantage of the dual‐functionality of MagDots, the magnetic force experienced by a single MagDot and the number of MagDots on MTs are determined. The total force exerted on MTs by MagDots is estimated to be ≈0.94–2.47 pN. This approach could potentially be used to interrogate MT properties and MT‐kinesin interactions, enhancing our biological understanding of this system and enabling further development of MT shuttles for nanotransport.

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