  Cooperative interactions among the binding of multiple signaling molecules is
a common mechanism for enhancing the sensitivity of biological signaling
systems. It is widely assumed that this increase in sensitivity of the mean
response implies the ability to detect smaller signals. We show that, quite
generally, there is a component of the noise in such systems that can be traced
to the random arrival of the signaling molecules at their receptor sites, and
this diffusive noise is not reduced by cooperativity. Cooperativity makes it
easier for real systems to reach this physical limit, but cannot reduce the
limit itself.
