What do you mean by huge? That could be visible by naked eye?

My speculation has to do with competition. It's possible that Nature might not have a problem engineering such a giant cell, but it might under-perform under conditions (sea, soil, jungle, etc) where metazoans can do way better and thus instead of using resources successfully, it might be a resource for other organisms. It gets eaten away. -

Valerio Bianchi: my question also stated:   "......cell is a large & independent individual - may be as big as a mouse, if not like a whale?"

Oscar Sierra: True, competition is one of the key-elements in 'natural selection'. But why is a giant cell expected to under-perform compared every metazoan? What would prevent it from using resources successfully? Can you please specify your reason(s)?

@ Kshitish : Imagine an experiment where you are co-culturing a microbe ( e.g. E.coli) and a giant cell (as big as mouse). to culture a giant cell the nutrient requirements will be higher by many folds than E.coli, so by the time the giant cells metabolize the nutrients to generate its optimum size, E.coli goes through several generation and reaches to higher cell number. The competitive fitness to cope with lack of nutrients will become tremendous on such giant cells, and in order to attain a large cell size it will consume most of its energy. Whereas the normal microbes might use it for cell division  and proliferation.  Unless the size of giant cells give the advantage for survival of the cell, it will loose the battle of existence to rapidly dividing microbes. So the unicellular gaint cell are uncommon but there are some rare exceptions like Xenophyophore which attains a size of 20 centimeters, interestingly it has cytoplasm with numerous nuclei.

Prashant: Why should lack of nutrients be a constraint specifically for a giant cell - particularly in a culture conditions. While it seems obvious that being a giant cell might put individuals to one or more disadvantages in terms of competition and/or routine survival - the question here is what specific cellular, molecular, biochemical, biophysical or design aspects might be causing such disadvantage(s)?

We could imagine anything. The giant cell eats all microbes and remains happy while all micobes vanish within the first hour of the culture! I can also imagine that while bacteria slow down nutrient consumption during reproduction, the giant cell grows faster by consuming most nutrients and hence bacteria eventually loose. Also, we are discussing any situation anywhere in space and time (on earth for now) - culture conditions will have limitations in terms of comparisons. But I understand your attempts to visualize one possible situation we are all familiar with.

Yes, there are a few exceptionally large cells within metazoan bodies (e.g., some nerve cells and eggs), and even rarer species such as Xenophyophore - but there has been no cell with a body mass comparable to that of even a mouse. Forget elephants, dinosaurs and whales!

It's quite simple really; surface area increases by the radius square and volume by cube. So if the volumes increases to the size to accommodate a mouse-sized cell, then the surface area would be so small that the cell would not be able to nether get rid of toxic by-products and generated heat nor be able to absorb enough necessary nutrients to carry out any viable biological processes.

Kshitish, in order to answer your question we would have to look specifically at every cellular mechanism and try to examine its design at larger dimensions. In some cases it might do well but not in othes. Take for example a cell the size of a mouse. Do you think the same 100-nm lipid bilayer membrane would be able to hold a 20-gram protoplasmic soup? Possibly not, and soon you’ll realize that in order to get a cell that size you’d have to change the typical eukaryotic cell design, possibly creating some kind of powerful exoskeleton for the cell to be able to hold the 20-gram soup without spilling. So let’s say that such a cell might look like a huge walled plant cell. Now, let’s say that the cell needs to respond to an extracellular stimulus, say food source, predators, or physical threats like heat or cold. A typical cell that uses cAMP, calcium currents, lipid messengers like IP3 or Na+ or K+ signaling might respond in milliseconds but for the baseball ball size cell, it might take 10 seconds to convey the signal through 2 inches of the aforementioned 20-gram thick soup. Now you have a cell that not only can easily break apart but also is slow to react. It might still work though but when you start to add up features, you need to grant further concessions and you end up with some really weird stuff. You might model it using computer models and it might still work in isolation but the only way to prove whether the design has relevance in the wild, is to do a field test. I’d suggest starting with computer models and if the design holds then testing it in the wild is the next step. By the way, all of this falls within a new discipline called Synthetic Biology. Good luck.

I agree with Oscar here. There is a cost for rigidity of cell wall or other equivalents (e.g., foraminifera) - particularly in terms of mobility restraints. Molecular transport is perhaps the biggest challenges though - this is what came to my mind (when the question was posed to me in an interview for a lecturer's position several years back). In fact, thoughts similar to what you wrote have been so convincing to me that I do not have to go for computational modeling.

Sohan's point also relates to molecular transport indirectly. But, I think, surface-volume relations as an explanation to cell volume/mass limit is not really that straight-forward or simple. I can certainly imagine ways to counter the ways to increase ways to absorb more nutrition and/or to excrete unwanted stuff. But again the obstacle is met by means of the need for managing a more efficient internal molecular transport system! 

I think, the limit to the ability to create more efficient internal transport system and also enhance the specific local molecular concentrations by 'compartmentalization' have been the key!

Elaborating: "I think, there has been a cellular limit to (a) create more 'efficient internal transport system' & also, (b) enhance the differential & localized molecular concentrations by 'compartmentalization'!"

Initially I used to imagine solving the problem with molecular transports via more-refined membrane networks (such as ER) or targeted vesicles (e.g., Golgi bodies). My current understanding is that 'compartmentalization' and 'complex transport mechanisms' for directed molecular transport are essential for most reactions inside the bigger cells. But there was a limit to the compartmentalization and large-scale transport within cells. This is perhaps the reason why the initial cells (e.g., prokaryotes) could not be bigger without endo-symbiosis-like events. Eukaryotes could be bigger, and be more efficient in many ways, by inner compartmentalization: which ensured (a) Division of labor across smaller pockets; (b) Better distribution of molecular concentrations (e.g., molecules for certain pathways stay only in mitochondria and DNA-associated processes happen in nucleus).

Such compartments not only separated molecules, but also brought in the required concentration of key enzymes in appropriate local areas. Molecular-transport was achieved by targeted vesicular transports. But further compartmentalization could not be achieved using the membrane system as this demanded new types of jobs - including mass-transport of nutrients  [e.g. stronger cell-wall-like structures were required inside and the 'transport or compartmentelization requirements' increased exponentially]. Multi-cellular  species could achieve this by building better transport systems: starting with simple water circulation as in the poriferans, and further division of labor. Of course, plants and animals have more elaborate systems as we know.

May be I wrote too much and people lost interest!?

Hi guys, I should like to add few more points

1) In general electron transport system (ETS) is not 100%, meaning it de-couples easily resulting in liberation of heat. This by-product has got to be rid of also;

2) You have been concentrating on nutrient uptake, structural and compartmentalisation, but such cell would also generate waste products (eg CO2) which also has to be efficiently disposed of;

3) Genetics also plays a role in determining the size of an organism too; this is perhaps as to why one does not see gigantic humans, carrots or amoeboid cells. So the genetics has to be re-engineered as well.

Of course genetics plays an important role in determining the size of an organism Sohan. But I don't see why or how that can be a limiting factor.

About waste disposal: true, that also becomes one of the important needs to be addressed. But that would also come down to the need for compartmentalization! To some extent plant cells have managed this by using internal vacuoles for storing some of the waste. But most other bigger eukaryotes have ended up using a separate/shared transport system (e.g. circulatory & respiratory systems). Such systems using simple lipid/protein-based compartments within the cells would be extremely difficult to build and manage!

..  and look what cells have learned to do in order to be big! http://www.sciencealert.com.au/news/20142607-25928.html 

I do wonder if the aspect of specialized cell-functions with large volumes, including the point of view of 'design' that enables long-distance molecular communications?

Interesting research: http://www.digitaljournal.com/science/why-are-cells-so-small/article/419849