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High-Throughput Magnetic Actuation Platform for Evaluating the Effect of Mechanical Force on 3D Tumor Microenvironment.

ABSTRACT: Accurately replicating and analyzing cellular responses to mechanical cues is vital for exploring metastatic disease progression. However, many of the existing in vitro platforms for applying mechanical stimulation seed cells on synthetic substrates. To better recapitulate physiological conditions, a novel actuating platform is developed with the ability to apply tensile strain on cells at various amplitudes and frequencies in a high-throughput multi-well culture plate using a physiologically-relevant substrate. Suspending fibrillar fibronectin across the body of the magnetic actuator provides a matrix representative of early metastasis for 3D cell culture that is not reliant on a synthetic substrate. This platform enables the culturing and analysis of various cell types in an environment that mimics the dynamic stretching of lung tissue during normal respiration. Metabolic activity, YAP activation, and morphology of breast cancer cells are analyzed within one week of cyclic stretching or static culture. Further, matrix degradation is significantly reduced in breast cancer cell lines with metastatic potential after actuation. These new findings demonstrate a clear suppressive cellular response due to cyclic stretching that has implications for a mechanical role in the dormancy and reactivation of disseminated breast cancer cells to macrometastases.

SUBMITTER: Enriquez A

PROVIDER: S-EPMC8577425 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We are reporting on the fabrication and characterization of microscale electromechanical actuators driven by the internal forces induced within the depletion region of a typical pn junction. Depletion region actuators operate based on the modulation of the interactions of the internal electric field and the net space charge within the depletion region of a pn junction by an external potential. In terms of performance, depletion region actuators fall between electrostatic actuators, where a physical gap separates the charges on two electrodes, and piezoelectric actuators, where the separation between the charges is on the order of lattice constants of the material. An analytic model of depletion region actuator response to an applied potential is developed and verified experimentally. The prototype micro-mechanical device utilized the local stresses produced by the depletion region actuators to generate mechanical vibrations at frequencies far below the resonance frequencies of the structure. A laser Doppler vibrometer was used to measure and compare the displacements and vibration patterns caused by the depletion region and electrostatic actuators. Utilizing depletion region actuators neither requires etching of narrow gaps, which is technically challenging nor is there a need for introducing piezoelectric materials into the fabrication process flow. The simple operating principle and the possibility of exploiting the technique for various optimized linear or nonlinear actuation at small scales provide opportunities for precise electro-mechanical transduction for micro- and nano-mechanical devices. These actuators are therefore suited for the co-fabrication of micro- and nano-mechanical systems and microelectronic circuits. Additionally, the produced strains depend only on the depletion region specifications and the excitation voltage and do not scale with device dimensions. As such, depletion region actuators can be candidates for efficient nanoscale electromechanical actuation.

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High-Throughput Magnetic Actuation Platform for Evaluating the Effect of Mechanical Force on 3D Tumor Microenvironment.

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