Micro-tool taps forces that shape living tissue

U. PENN (US)–Bioengineers have developed a micron-sized device to measure and manipulate forces at work as living cells form tissue. The tool could help scientists study irregular or diseased tissue, such as beating cardiac tissue.

Chris Chen, professor of bioengineering at the University of Pennsylvania and the study’s chief author, developed the device with colleagues at the University of California, Santa Barbara and the University of Cambridge. The findings were published in the June issue of the Proceedings of the National Academy of Sciences.

The push-and-pull of cellular forces drives the buckling, extension, and contraction of cells that occur during tissue development, which are essential for wound healing and tissue homeostasis in adult organisms.

Yet a detailed picture of how tissue mechanics link to an organism’s development has been hindered by a lack of model systems in which both mechanics and remodeling can be simultaneously examined.

The new device applies technology currently used to craft semiconductors. Scientists fabricated an array of tiny divots within a mold and immersed the mold in a culture of cells and collagen and then placed raised microcantilever posts on either side of the mold and—much like draping a volleyball net across two metal poles—observed the formation of a cell and collagen web of living tissue anchored to the cantilevers.  They were then used to simultaneously constrain the remodeling of a collagen gel and to report forces generated during this process.

“Just as we build muscle in the gym, these same mechanical forces are translated down to the cellular level and build the complex arrangement of different tissues in the body,” coauthor Wesley Legant explains. “By varying the properties of our model system, we can study how these mechanical factors are distributed throughout a tissue and how this can, in turn, effect cellular function.”

The system will allow researchers to test new pharmaceuticals against a large array of small tissue samples, Chen says, and possibly identify new ways to increase the contractility of cardiac muscle or to relax arteries to treat hypertension.

The research was funded by grants from the National Institutes of Health, an Army Research Office Multidisciplinary University Research Initiative, the Material Research Science and Engineering Center and Center for Engineering Cells and Regeneration at Penn, U.S Department of Education’s Graduate Assistance in Areas of National Need, and the National Science Foundation’s Graduate Research Fellowship.

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