Size and Scaling

How cells sense their size, or whether they sense it at all, remains a fundamental open question in biology. We discovered that during mitosis, the wavelength of cortical waves, which is determined by the oscillation frequency, scales with cell size (Xiao et al., Developmental Cell, 2017). To our knowledge, this was the first experimental demonstration of such a relationship. This scaling behavior depends on a unique property of the mitotic cortical waves where changes in the oscillation period occur independently of wave propagation speed. This is different from what is seen in classic reaction-diffusion systems.

Our studies revealed how this decoupling can be achieved. We found that the oscillation frequency can be tuned by adjusting the level of phosphatidylinositol-3 kinase (PI3K) on the plasma membrane (Xiong et al., Nature Chemical Biology, 2016), while the speed of wave propagation is controlled through curvature-dependent mechanochemical coupling (Wu et al., Nature Communications, 2018). These insights point to a previously unrecognized mechanism by which cells can encode spatial and size information, helping to guide important decisions during mitosis. This research opens an exciting direction in understanding how cell growth is coordinated with division, which is now a major focus in our lab.

Another long-standing question is whether mammalian cells have a size checkpoint that links cell growth with cell cycle progression. Addressing this in mammalian cells has been difficult because mammalian cells often have irregular shapes, and it has been challenging to measure their size accurately. To overcome this, we designed a PDMS-based microchannel system to physically constrain cells in three dimensions. When grown in these channels, cells adopt a cylindrical shape and grow and divide similar to rod-shaped bacteria (Varsano et al., Cell Reports, 2017).

Using this confinement system, we provided the first experimental support for a phenomenological model of cell size homeostasis in mammalian cells, known as the "adder" model. This model suggests that cells grow by adding a constant size between birth and division, regardless of their starting size. We are interested in how adder behavior is regulated or manipulated.