Cells shift shapes to crawl faster in gooey fluids than in watery ones

By staring at movies of cell migration for hours, we realized cells have a mechanosensor, membrane ruffles, to test viscosity and trigger adaptation
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Our project started as a simple exercise for new students in the lab to practice microscopy skills - recording cells moving around for hours. To make it more fun, we decided to immerse cells in very viscous medium, fully expecting to see cells slowing down as they try to migrate in the medium with viscosity 2000-times stickier than water, or regular medium used in the lab.

We were surprised that cells moved twice faster in the viscous medium.

Scratching our heads, we went back to make more movies to look at. This time the movies were acquired at higher resolution. We watched many movies acquired using different techniques, including interference reflectance microscopy (IRM), fluorescence, and bright field. We found that when the viscosity increases, the the frilly membrane structures, known as ruffles, at the cell edge disappear, cell spreads out, and the contact points between the cell and the substrate, known as focal adhesions, start to form rapidly.

The movie below shows our typical observation, where focal adhesion grows explosively (left),  cell spread area expands (center), and membrane ruffling stops (right) after viscosity increases.

A 3D view of how a cell responds to increased viscosity gave us more appreciation how cells sense and respond to high viscosity. Cell membrane originally moves up and down when the cell is immersed in regular medium, and upon viscosity increase, the membrane stops moving and the cell becomes flat, with the spread area increases simultaneously. 

After many tests, we concluded the counter-intuitive speed increase that surprised us is due to viscous drag. The extremely high viscous drag prevents the plasma membrane from ruffling up and down as in regular medium, thereby redistributing the membrane originally stored in the ruffles, resulting in a 2-fold increase of spread area, formation of more focal adhesions which facilitate faster cell migration.

Our model can be summarized in the following figure.

We are curious regarding how altered viscosity in human bodies affect cells. For example, mucus becomes more viscous in patients with chronic lung diseases such as cystic fibrosis. Tumor microenvironment also exhibits high fluid viscosity. Does high viscosity make cells act differently in those diseases and cause more damages in the tissue? We hope to solve this mystery in the near future.

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