A Magnetic Micromanipulation System for Intra-Cellular and Intra-Tissue Mechanics

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To reveal the mechanics and functions of intracellular structures and organelles demands direct mechanical measurement inside a cell. Compared to conventional cell mechanics performed from outside the cell, intracellular mechanical measurement is underexplored. Similarly, few attempts have been made to measure the mechanics within bulk tissue (vs. on tissue surface). It is well recognized that cells in vitro migrate towards the stiff region of a substrate, a process termed durotaxis. However, experimental measurement of durotaxis inside tissue remains lacking.******This RTI application requests a magnetic micromanipulation instrument with unique capabilities of moving magnetic microbeads inside single cells or deep inside a tissue to obtain accurate force-deformation data for intracellular and intra-tissue mechanics characterization. The magnetic micromanipulation instrument contains eight magnetic coils placed on different planes to generate 3D magnetic fields. It has two operation modes: (1) the use of six of the eight magnetic coils to generate a strong magnetic field gradient for moving a micrometer-sized magnetic bead and applying forces up to 200 pN, which will be used for our proposed intracellular mechanics work; (2) the use of the eight magnetic coils to generate uniform magnetic field gradient for applying the same force on all the magnetic beads within the workspace, which will be used for our proposed intra-tissue mechanics work. In experiments, magnetic microbeads and cellular structures will be fluorescently labelled, and their displacement/deformation will be measured by fluorescence microscopy imaging. ******Our HQP will use the requested equipment to perform mechanical measurement inside individual cells, mechanically load intracellular structures to induce mechanotransduction responses, and achieve mechanical measurement deep within tissue. The equipment will be used to train a high number of postdocs and graduate students who will gain skills in cell and tissue mechanics, cell mechanotransduction, development biology, microscopy imaging, and precision instrument control and measurement.