The establishment of cell culture systems opened the door to an unparalleled revolution in biomedical science, but this common lab practice remains drastically artificial and is often not translatable to real-life in vivo systems. This limitation is particularly notable in efforts aiming to understand the mechanisms regulating responses of cells and tissues to mechanical forces in their natural environment. A new technique developed by a team from Harvard aims to overcome these limitations by better simulating life-like stretching in a culture dish.
The team developed a hybrid material consisting of a light-sensitive soft hydrogel surrounding an embedded array of microplate platforms. Cells grown on this material tightly grasp onto the tips of the microplates. To stretch these adhered cells, the hydrogel is briefly heated with a focal laser pulse, leading it to contract. This contraction pulls on the adjacent microplates and, by extension, the adhered cells.
This cartoon explains how a focal laser light pointed at an area of the photo-responsive hydrogel causes it to locally contract, passively pulling at the embedded microplate tips and the cell structures attached to them. As shown in the top view of the hydrogel pictured in the clip, the displacement of the microplate tips in local areas happens fast and is entirely reversible. Credit: Wyss Institute at Harvard University
Given the easy and reversible manipulation with a mere light pulse, this technique is safe to use with cells and exerts forces that are physiologically relevant. In contrast to typical manipulation techniques that are less dynamic or require the manipulation of entire sheets of cells, this highly-controllable culture system enables deformations ranging from full sheets to single-cell stretching. By varying the microplate patterns and dimensions, applied forces can even be optimized for culturing cells from different tissue sources.
While this platform is still limited to a 2D-culture environment, it provides a significant improvement over the typical stagnant cell culture approaches used in research on a daily basis. By offering a non-invasive method to apply physiologically-relevant forces to samples of interest, this work promises to improve our understanding of cell movement, cell-to-cell interactions, and the progression of diseases such as muscle wasting or cancer metastasis.
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