Physical limits of cells and proteomes
Ken A. Dilla,1,2,
Kingshuk Ghoshb,2, and Jeremy D. Schmitc,2,3
Author Affiliations
aLaufer Center for Physical and Quantitative Biology and Departments of Physics and Chemistry, Stony Brook University, New York, NY 11794;
bDepartment of Physics and Astronomy, University of Denver, Denver, CO 80209; and
cDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143
Contributed by Ken A. Dill, September 2, 2011 (sent for review August 10, 2011)
Abstract
What are the physical limits to cell behavior? Often, the physical limitations can be dominated by the proteome, the cell’s complement of proteins. We combine known protein sizes, stabilities, and rates of folding and diffusion, with the known protein-length distributions P(N) of proteomes (Escherichia coli, yeast, and worm), to formulate distributions and scaling relationships in order to address questions of cell physics. Why do mesophilic cells die around 50 °C? How can the maximal growth-rate temperature (around 37 °C) occur so close to the cell-death temperature? The model shows that the cell’s death temperature coincides with a denaturation catastrophe of its proteome. The reason cells can function so well just a few degrees below their death temperature is because proteome denaturation is so cooperative. Why are cells so dense-packed with protein molecules (about 20% by volume)? Cells are packed at a density that maximizes biochemical reaction rates. At lower densities, proteins collide too rarely. At higher densities, proteins diffuse too slowly through the crowded cell. What limits cell sizes and growth rates? Cell growth is limited by rates of protein synthesis, by the folding rates of its slowest proteins, and—for large cells—by the rates of its protein diffusion. Useful insights into cell physics may be obtainable from scaling laws that encapsulate information from protein knowledge bases.
cell biophysics, protein dynamics, protein stability, diffusion and folding, proteome modeling
Footnotes
1To whom correspondence should be addressed. E-mail:dill@laufercenter.org.
2K.A.D., K.G., and J.D.S. contributed equally to this work.
3Present address: Department of Physics, Kansas State University, Manhattan, KS 66506.
Author contributions: K.A.D., K.G., and J.D.S. designed research and wrote the paper.
This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2008.
The authors declare no conflict of interest.
Freely available online through the PNAS open access option.
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