今天看了這一系列研究方向的新進展。
你相信細胞會因為你怎麼「拉扯他」而發育成不同的細胞嗎？
2003年，Farge發現把果蠅的胚胎輕輕的用玻璃壓住，結果一個叫做twist的基因就這樣被啟動。Farge進一步發現，胚胎在扭曲形變的過程中，組織的壓迫會使得這個基因在腸子表現。
是基因啟動形狀還是形狀啟動基因?
我很喜歡的一本書是On Growth and Form, 挑戰「內在元素」決定生命型態的論點。然而作者是相當極端的外在論派，因此在基因發現之前寫的主張，就像Gibbens的極端心智外在論在認知神經科學發展的現在，被現視為舊時代的思想。
但是有了這樣的學說的洗禮，才有可能跳脫現金完全內在論的生命與心智世界。
Farge的研究推翻了型態完全由基因決定的說法，找到證據說明型態是如何啟動基因，兩者間是互相共同發展的，沒有誰先誰後。
"The genome must be aware at key stages of the shape it is in charge of developing." says Farge.
Farge認為這是tissue compression的基因與twist gene的控制基因（兩者會在不同的肌肉群中表現，因此原本不會有任何關係的）之間的間接互動方式，然而雖然Farge找到的互動例子是兩個基因所決定的性狀，事實上應該還要有非基因決定的物理條件會影響細胞的發展型態。
Ingber發現，細胞會對「物理的拉扯力」起反應而發展出不同的性狀。
"[Ingber's] findings are remarkable.Pull a stem cell in one way and it starts developing as a brain cell, stretch it in another, and a bone cell is its more likely fate. Change the mechanical stresses on cancer cells and they can start to behave more like healthy ones. "
我臉拉對方向就會變成美女嗎（>////<)？物理力的作用就在此呈現。然而...
物理力是透過什麼樣的機制去影響基因的？
Cytoskeleton是一個答案。
現在已經知道，cytoskeleton的組織會偵測細胞處在的extracellular matrix性質，這包括「堅硬的」、「有彈性的」、「充滿張力」或者「受傷」。根據這些不同的性質，幹細胞可以在沒有growth factor的情況下分化成不同的組織細胞。
"on a relatively soft base that resembled the sponginess of brain tissue, stem cells began to form the precursors of neurons; on stiffer, muscle like substrates the cell took steps toward froming muscle stem cells..."
而cytoskeleton本身是如何因應環境性質，面對不同物理環境所展現出來的張力、伸縮等結構力學改變，正是現在生物學正逐漸熱門的領域。
與2005年的連結...
2005年，我在生科系報告了一篇cell 經典文章:
Streuli CH, Bailey N and Bissell MJ (1991). Control of mammary epithelial differentiation: Basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity.
關於這篇我有在另一個文章裡談過。
有趣的是關於今天這個發現的連結。
"Mammary cells grown in soft gels organized themselves into structures characteristic of normal breat tissue, whereas cells grown in stilff 'cancerous' gels did not. "
Weaver與Bissell的差異是Bissell發現失去某些化學分子的extracellular matrix會導致細胞癌化與否，而那些化學分子反應的是細胞與細胞之間的互動關係使否正常。但是Weaver不一樣。他們改變的是gell本身的物理性質。
"They found that the stiff gels pulled more on the membraine-spanning integrins, and this boosted the activity of an integrin-conotrolled signalling pathway that regulates tension in the cytoskeleton."
酷吧。
醒醒吧molecular biologists...
"Then, as now, most cell biologists had little time for architecture and engineering. When they want to understand why a cell behaves the way that it does, they try to identify the genes, proteins and signalling molecules that are thought to exert control."
許多細胞學家不屑數學與物理對於生物學會有的幫助，只相信基因、蛋白質等分子控制細胞的能力。
Wilhelm His (1888) "to think that heredity will build organic beings without mechanical means is a piece of unscientific mysticism. Astronauts' bones get thinner when they escape gravity. Hefting weights inflicts physical damage on muscle cells that stimulates them to grow. But it was widely felt that the role of mechanical stress would be limited to these and other cell types that needed it in order to function normally."
Wilhelm在1888年就道破（雖然比on growth and form晚）這個迷思，現在這個領域已經火熱的在nature上討論著，台灣的科學家心態改變了嗎？
References:
Stretching the Imagination, Nature News Feature, 456, Dec. 2008
On Growth and Form by D'Arcy Wentworth Thompson
Nature上有一系列的文章都在玩這概念，就附在這邊等我有空再讀囉。
Abbott, A. Cell culture: Biology's new dimension,Nature 424 (2003)
Powell, K. Stem-cell niches: It's the ecology, stupid! Nature 435 (2005)
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