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Future Therapeutic Strategies May Depend on Creative Scientific Approaches Today

Before any scientific question can be answered, it must be dreamed up. What happens to cause a healthy cell or tissue to change, for instance, isn鈥檛 fully understood. While much is known about chemical exposures that can lead to genetic mutation, damaged DNA, inflammation and even cancer, what has rarely been asked is how physical stressors in the environment can cause a cell or tissue to respond and adapt. It鈥檚 a piece of the puzzle upon which future medical breakthroughs might depend.

Homeostasis refers to a state of equilibrium; at the cellular and tissue level, any changes in environment will spur a response that balances or accommodates it. 鈥淢ostly people think of chemical changes, exposure to drugs, for instance,鈥 says Schwarz, principal investigator on the project. 鈥淗ere we ask, what if you squeeze a cell鈥攐r a group of cells or tissue鈥攎echanically? Can it still carry out its functions? Maybe not. Maybe it needs to adapt.鈥

听补苍诲 , both professors in the 听补苍诲 members of the聽, have been awarded a four-year National Science Foundation grant from Physics of Living Systems, for a project titled “.”

Two headshots of people side by side
From left, Alison Patteson and Jennifer Schwarz

As co-principal investigator Patteson notes, describing the idea this way is a new use of scientific language. 鈥淎s physicists, we are proposing this idea that there is a mechanical version of homeostasis,鈥 she says. 鈥淲e have proposed a framework for that.鈥

Drawing upon previous collaborations that have examined specific scales (such as chromatin molecules, individual cell motion, and collective cell migration through collagen networks), the investigators will work to build a multiscale model to capture how chromatin remodels from physical stressors at the cell- and tissue-level. They will conduct experiments involving mechanical compression, and working with the聽, observe detailed microscopic images of the cells in action.

Fluorescence microscope image of a cell amidst fibrous structures, displaying vibrant colors with a scale bar indicating 50 micrometers.
3D reconstruction of a collection of cells, called a cell spheroid, with individual nuclei in yellow. This is an example of a detailed microscopic image used to study cell motility. (Photo credit: Minh Thanh of the Patteson Lab and Blatt BioImaging Center)

Understanding these mechanisms may have broad implications in health research, shedding light on the causes of and therapeutic treatments for inflammation and potentially, cancer.

鈥淲e know that most cancerous tissues get stiffer,鈥 says Patteson. 鈥淭hat鈥檚 how you identify it. There鈥檚 clearly a change in mechanics associated with the development of the disease.鈥

But much remains to be discovered about the interactions and processes at different scales. 鈥淲e鈥檙e not at therapeutic levels yet,鈥 says Schwarz.

The professors note that creativity is essential to this stage of research鈥攊n imagining what might be possible and what new questions to ask, and in pushing the boundaries of existing scientific language. To that end, they have incorporated broader outreach between the physics and creative writing departments in their project.

In a collaboration with creative writing professors聽听补苍诲聽, along with M.F.A. candidate聽, students from both departments will cross over and embed in their respective classes. 鈥淸They鈥檒l see] how a piece of poetry is creative, for example. Then, how a certain experiment is creative,鈥 says Schwarz. 鈥淲e want to get physicists thinking like creative writers, and vice versa.鈥

The colleagues like to think that students and their work will benefit from the exercise, not only in expanding their ideas of what is possible but also in taking a more thoughtful approach to the language they use. Instead of talking about hierarchy of scales,鈥 says Patteson, 鈥渕aybe we should be talking about coupled things, or partnerships.鈥 A simple shift in perspective, after all, can sometimes put things in a whole new light.

Story by Laura Wallis