What determines a cell's shape might not seem a particularly pressing question. But biochemist Julie Theriot explains that, for those eukaryotic cells that don't have a cell wall, shape is intrinsically connected to the inner mechanics that facilitate cell movement. By combining a large-scale study using microscopy with mathematical modelling, her group has determined that for certain cell types, shape — and thus movement — is determined by an interplay between membrane tension and the distribution of actin filaments, chief components of the cell's scaffolding.

Theriot, who is based at Stanford University School of Medicine in California, confesses to a lifelong fascination with moving cells. “I was that kid who would scoop up pond water to look at all the swimming critters under a microscope,” she says. That fascination carried through to her graduate studies in the early 1990s, when she began studying actin dynamics in moving cells.

After another group showed that cultured fish keratocytes — cells found in fish scales — move in a persistent manner, with a wide leading edge and a rounded cell body bringing up the rear, Theriot trekked down to the local pet shop to buy some goldfish. Others in the field, including her graduate advisor, Tim Mitchison of Harvard Medical School in Cambridge, Massachusetts, went on to propose in the mid-1990s that keratocytes' movement was driven by 'treadmilling' of the actin network.

After spending a number of years studying actin in other cell types, Theriot recently returned to keratocytes to test the idea that the cells might be shaped by their movement. The study on page 475 reports her group's assessment of the natural variation in shape among keratocytes and in the density and location of their actin filaments. To gather a large enough dataset, four of the authors spent nine months at the microscope, between them recording and measuring about 2,000 individual cells. The group showed that 93% of shape variation can be captured by measuring just two parameters: the cell's area and whether it has a rounded 'D' shape or a more elongated 'canoe' shape. In addition, they found that the area occupied by an individual cell is essentially constant whatever its shape, limited by the cell's unstretchable membrane.

With this information to hand, the team derived a mathematical model, starting with the assumption that membrane tension limits cell shape, and incorporating the two main parameters that explain the shape. According to the model, where filament density is highest, actin grows at a rate that overcomes membrane tension, so protrusion occurs at the leading edge of the cell. At the other end, where filament density is low, the membrane tension causes collapse of the actin filaments, which draws in the rear.

Theriot embraces the applied mathematics involved in the work. “The whole reason for my existence is to make cell biology a more quantitative science,” she says. Finding simple quantitative relationships between cellular components leads to much richer insight into mechanisms than studies that look only for the absence or presence of a trait, she adds.

And although understanding cell shape has important implications for work on processes such as wound healing, immune responses, development and cancer metastasis, Theriot's interest also stems from a more basic curiosity. She is intrigued that although eukaryotic and bacterial cells both contain the same basic components, only eukaryotes developed a range of wildly complicated shapes.