The Stopak-Harris Theory to explain embryonic formation of tendons, ligaments, skeletal muscles, artery walls, organ capsules and maybe other structures, too.

(Note: this is NOT the same as the Murray-Oster (et al.) biomechanics theory, and has no relation to Malcolm Steinberg's Differential Adhesion Hypothesis DAH either. Malcolm liked this one, and encouraged me a lot about it.)

Nor am I trying to convert you to support or oppose any particular theory.

The key points are:

* Nobody knows what mechanism lines up collagen and cells to build these structures.
* David Stopak and I published a Nature paper proposing a mechanism, with evidence.
* We and others have published other evidence, pro and con.
* It has gotten into the unabridged edition of "Molecular Biology of the Cell"
* But has been removed from a couple of Developmental Biology textbooks.
* In a few countries, it gets taught as fact. (Not the US, however)
* If the theory were true, it would be a big deal.

* David Stopak and I are not holding our breath waiting for any calls from Stockholm.

* Is it a good framework for discussing how theories get accepted, rejected or hijacked?


What were the original paradoxes?

A) Type I collagen gets geometrically arranged into many different geometric patterns.
(Lots of people noticed this, were surprised + wrote about it)

B) Crawling fibroblasts exert a 100-times stronger forces than needed for locomotion.
(David and I discovered this, ourselves; but others confirmed it.)


What was the evidence?

a) Cells wrinkling rubber, lining up collagen up to 6 cm. distances.

b) Isolated rat collagen, fluorescently labeled & injected into embryos gets rearranged
(To form tendons, ligaments, walls of arteries, muscles) David +Norm Wessells did this.)

c) Tissue cultures of leg bones (cartilages) line up collagen gels & muscle cells. (David did this, too)

Contradictory evidence (perhaps disproof) from a German Lab. Mutations, that greatly weaken cell traction and inhibit wound contraction, nevertheless do not inhibit formation of tendons, muscles. We should find the citation to this paper. A student last year found it by Google Scholar. The Germans referred to the Harris/Stopak Dogma, which they "confronted".


What did David and I propose, to explain observations and paradoxes?

* Some differentiated cells use traction to move themselves, but the main function of traction exerted by fibroblasts is moving collagen past cells.

* That is why fibroblast traction is so ridiculously, excessively strong.

* That's how type I collagen gets arranged into so many different geometries.


What additional evidence is needed either to prove we were right? Or that we were wrong?


How can so many different muscles be formed by such a simple mechanism?

Why don't other differentiated cell types (besides skeletal muscle cells) also get arranged into the same geometric patterns as muscles?

Why does collagen (and smooth muscle cells) get wrapped around blood vessels, but collagen (and skeletal muscle cells) get aligned along axes (e.g. instead of around)?




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