May 11, 2019 | David F. Coppedge

Extreme Fine Tuning in Body Cells, Part 2

Here are two examples of an ultra-fine balance between function and disease inside the cells of our body’s sensory cells (Part 2).

Microtubules

A finely-tuned balance exists in our cells between health and terrible diseases. That balance exists in the cellular “skeleton” called the microtubule network. Microtubules are linear tubes made up of the building block proteins tubulin-alpha and tubulin-beta. Microtubules grow and shrink as needed, providing pathways for molecular motors to carry cargo. They also provide structural integrity for the cell. If these microtubules are too flexible, horrible diseases can result, like Huntington’s disease, Parkinson’s disease and AMS. “On the other hand, elevated levels of αK40 acetylation promote cell–cell aggregation, migration, and tumor reattachment in multiple aggressive, metastatic breast cancer cell lines.” Not good. What keeps the amount of flexibility vs stiffness ‘just right’ to prevent disasters like these?

Microtubules (straight lines) are built of tubulin proteins. Credit: Illustra Media.

Scientists writing in PNAS looked into this, and found that the tubulin building blocks need to be “acetylated” (connected to tiny acetyl groups, C2H3O), in order to provide the proper amount of stiffness. Moreover, the cell can tune the stiffness of subunits with acetylation in order to provide just the right amount of flexibility:

Our high-resolution maps serve as a blueprint for the scale of conformational change and relevant degrees of freedom that the αK40 loop can sample. We show that acetylation of tubulin induces electrostatic perturbations that restrict the motion of the αK40 loop, weakening lateral contacts [which is good]. The sum of many weak reduced lateral contacts reduces the inter-PF interactions. The increased flexibility provided by fewer inter-PF [protofilament] interactions provides a mechanism by which αTAT1 can locally fine-tune the load-bearing capacity and mechanical resistance to stress of MTs [microtubules]. Deacetylation increases lateral contacts, which renders MTs inflexible, brittle, and highly susceptible to breakage under stress. The pattern of increased lateral interactions between subunits leading to mesoscale instability may be conserved in other polymeric systems. Therefore, αK40 acetylation may function as an evolutionarily conserved [i.e., unevolved] “electrostatic switch” to regulate MT stability. Cancer cells may exploit this subtle form of regulation to promote cell adhesion, invasive migration, and other markers of aggressive metastatic behavior. [Bracketed words added]

The acetylation of tubulins was known beforehand, but scientists did not know if it was a simple association or a cause of the stiffness of microtubules. Now, they confirmed that acetylation causes healthy flexibility. Acetylation is a “post-translational modification” of the tubulin building blocks after the tubulin proteins are assembled by the ribosome. The act of acetylation is performed by other molecular machines. All of these are under quality control mechanisms using additional machines. In other words, this is an irreducibly complex system. When any part of the system breaks down, terrible things happen.

These are just two examples (see also yesterday’s post). Other instances of exquisite fine tuning in the body could be multiplied. Both papers say that similar systems involving ion channels or transportation networks likely have their own appropriate mechanisms to maintain tolerances within strict levels. Notice that these are all-or-none situations. In the ear, without the appropriate springiness of the tip link protein, dynamic control would be lost: all sounds would be heard at the same level, or not at all. In the cellular skeleton, without the appropriate stiffness brought about by acetylation, people would die of cancer or waste away with degenerative diseases. Think about these awesome wonders in your body that you probably didn’t even know about till now. Aren’t these causes for worship and gratitude?

The Joker: Chuck-in-the-Box

Evolutionists, please stop the nonsense that these systems are “evolutionarily conserved.” Do you really expect us to believe that evolution brought about these and a thousand other irreducibly complex systems in the first place? And do you expect us to believe that the inexorable force of natural selection (the Stuff Happens Law) failed to act once they “emerged”? That’s absurd. An “evolutionarily conserved electrostatic switch”— good grief. Electrostatic switches are made; they don’t just happen by chance. Microtubules are intelligently designed wonders from their first appearance. They surpass human understanding. We don’t need the Darwin Party to insert Charlie D’s hairy face into the story, like some Chuck-in-the-Box joker scaring the children. Stuff it, OK? Honor the Designer who made these systems.

 

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