Cell Size

What regulates cell size? The most obvious features of cells is that they come in a variety of sizes and shapes.  The next most obvious feature is that generally cells of the same type, eg. blood cells, epithelial cells, liver cells are generally close in size.  Within a species this is maintained.  Tall people and adults have more cells not larger cells than short people or infants.  The question of what maintains cell size, what causes it to vary, whether cell size is actively maintained or a passive outcome of other processes has recently been reconsidered, as an important and unsolved problem in biology.  We have approached this in systems and with several approaches. 

Question 1

The maintenance of cell size in dividing mammalian cells.  Why does the variance in size of cells in the  population remain the same in the setting of size dependent growth?

Question 2

What signaling pathways do cells use to control their size?

Is there a requisite linkage between growth rate and division rate or can that linkage be undermined by specific drugs.

To answer these questions we have co-developed, developed and collaborated on a number of new mathematical and biophysical methods, such as SMR (single microchannel resonator) with Scott Manlis at MIT, stimulated Raman spectroscopy with Sunney Xie (Harvard), quantitative phase microscopy, and ergodic rate analysis.  These give very accurate measures of size, mass density, rates of growth, rates of protein synthesis and rates of protein degradation.  We have shown that there is a feedback that maintains the size distribution of cells and  that the feedback acts on the rate of passage through the cell cycle and on the rate of protein accumulation.  We have a particular interest in the Tor pathway and the Hippo pathway.