Physical limits of cells and proteomes
Physical limits of cells and proteomes
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DOI：
10.1073/pnas.1114477108
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发表时间：
2011-11-01
影响因子：
11.1
通讯作者：
Schmit, Jeremy D.
中科院分区：
文献类型：
--
作者：
Dill, Ken A.;Ghosh, Kingshuk;Schmit, Jeremy D.
细胞行为的物理限制是什么？通常，物理限制主要由蛋白质组（细胞的蛋白质补充）决定。我们将已知的蛋白质大小、稳定性以及折叠和扩散速率与蛋白质组（大肠杆菌、酵母和蠕虫）的已知蛋白质长度分布 P(N) 相结合，以制定分布和缩放关系，以解决细胞物理学问题。为什么嗜温细胞在50℃左右会死亡？最大生长速率温度（约 37 摄氏度）为何如此接近细胞死亡温度？该模型表明，细胞的死亡温度与其蛋白质组的变性灾难同时发生。细胞之所以能在仅比其死亡温度低几度的温度下如此良好地发挥作用，是因为蛋白质组变性非常配合。为什么细胞中的蛋白质分子如此密集（约占体积的 20%）？细胞的堆积密度可以最大限度地提高生化反应速率。在较低密度下，蛋白质碰撞很少。在较高的密度下，蛋白质在拥挤的细胞中扩散得太慢。是什么限制了细胞大小和生长速度？细胞生长受到蛋白质合成速率、最慢蛋白质折叠速率以及（对于大细胞）蛋白质扩散速率的限制。对细胞物理学的有用见解可以从封装蛋白质知识库信息的标度定律中获得。
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 degrees C? How can the maximal growth-rate temperature (around 37 degrees 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.