Friday, August 9, 2024

Creation Moment 8/10/2024 - Design Patterns SERIES: Behavioral Design Patterns

Where is the wise? 
where is the scribe? 
where is the disputer of this world? 
1 Corinthians 1:20

"Behavioral design patterns focus on the dynamics of reaction networks. Andrews et al. identify eight such patterns. 
For example, there is switching, which occurs when a continuum of input needs to be converted into a discrete output. 
The most common ways of accomplishing this are by using ultrasensitivity or bistability

Ultrasensitive switches facilitate a sharp threshold response, ensuring that the system is fully in one state or the other, rather than in an intermediate state. This can be accomplished in different ways. A classic example of ultrasensitivity in biology is the necessary
switch of hemoglobin from binding oxygen in the lungs to releasing it in the muscles. This is performed through the allosteric design of hemoglobin. When the partial pressure of oxygen is high (in the lungs), binding of one molecule of oxygen makes binding of the next oxygen molecule easier. Importantly, when one plots the percentage of hemoglobin bound to oxygen versus the partial pressure of oxygen, the curve is sigmoidal, not hyperbolic. The sigmoidal shape tells us that in the lungs, binding of oxygen is easier after the first molecule binds and release of oxygen becomes easier in the muscle after the first molecule is let go.

Ultrasensitivity, represented by that sigmoidal curve, can be accomplished in another way. Suppose there is a phosphorylation-dephosphorylation cycle where the kinase and phosphatase are working at saturation levels and have rate constants that are independent of the concentration of their substrates. Although it isn’t abundantly clear until this is plotted graphically, the response is also ultrasensitive, i.e., sigmoidal. Given those conditions, the cycle can switch sharply between being almost entirely in one state to being almost entirely in the other state. (Ferrell and Ha 2014b)
Another way ultrasensitivity works is by having multiple phosphorylation sites on a kinase where the kinase isn’t active until the final phosphorylation, and each successive phosphorylation is a little bit easier than the prior one. (Ferrell and Ha 2014a)

A final and somewhat different example is positive feedback. This occurs more frequently in developmental networks than in sensory networks
Q: Why is that the case? 
Positive feedback slows response time, which is advantageous for
multistage processes that are time-consuming or include delays. Slower response times can also help reduce noise, which is critical when making irreversible decisions. However, positive regulation can accomplish more than just that. Positive regulation can make sharp decisions between two states and remembering those decisions for a long time, a phenomenon known as
bistability
Consider positive feedback in gene regulation: once a gene is activated by positive autoregulation, it is locked ON. 
The gene will remain elevated even after the input has disappeared, providing long-term memory that the input existed. This type of switching is employed during development to make irreversible decisions that commit a cell to a specific fate. (Alon 2019)

Q: Why does the switching design motif point to intelligence? Designing an effective switch requires understanding the system and what needs to be controlled “— what needs to be turned on or off at what time?” 
Considering whether control should be manual or automated is needed. Additionally, building appropriate switches requires knowledge about safety. 
Switching is also often necessary in sequential operations. 
The type of switch
the sensitivity of the switch
the construction of the switch
and the switch’s compatibility 
must all be thought through ahead of time. 
Each switch functions a certain way in the system such that it appears to “know” or “anticipate” other switch behavior so that more complex behavior can be produced.

Accordingly, design patterns in cells also provide an outstanding illustration of how design-based thinking can further our understanding of biology."
EN&V/EmilyReeves