細(xì)胞間連接在通信,、運(yùn)輸、信號(hào)轉(zhuǎn)導(dǎo),、廢物清除和水平衡中發(fā)揮著重要作用,。在一個(gè)歐洲項(xiàng)目中，研究人員研究了生物物理力量如何能夠影響這一系列功能的實(shí)現(xiàn),。
幾乎在所有組織中,，細(xì)胞間通信和信號(hào)轉(zhuǎn)導(dǎo)是通過(guò)縫隙連接(gap junction)或細(xì)胞間通道來(lái)實(shí)現(xiàn)的?？p隙連接是由成對(duì)的半通道(half-channel)或者說(shuō)連接子(connexon)組成的,，其中每個(gè)連接子含有由六個(gè)連接蛋白(connexin)集合在一起而形成的組裝體。盡管縫隙連接的功能和化學(xué)組分已經(jīng)得到很好地描述,，但是人們對(duì)這些結(jié)構(gòu)能夠支撐的力量和能量知之甚少,。
這個(gè)“生物物理測(cè)定縫隙連接的粘附強(qiáng)度”項(xiàng)目旨在利用高級(jí)納米工具和原子力顯微鏡(atomic force microscopy, AFM)來(lái)測(cè)量細(xì)胞間連接的動(dòng)力學(xué)和結(jié)合強(qiáng)度。項(xiàng)目研究人員在重建的脂質(zhì)膜中,，利用純化的連接蛋白來(lái)獲得關(guān)于細(xì)胞間結(jié)合方面的生物物理學(xué)證據(jù),。
項(xiàng)目研究人員在相互作用的蛋白分子上施加力量，并測(cè)量它們的解離特征,。一種快速的解離速率表明存在動(dòng)態(tài)結(jié)合,，而一種緩慢的解離速率反映著模擬胞外環(huán)的特殊構(gòu)造結(jié)構(gòu)的靈活性和大小降低。這個(gè)項(xiàng)目的研究結(jié)果于2012年7月13日在線發(fā)表在Journal of Molecular Biology期刊上,。
從生物物理學(xué)角度描述縫隙連接中的蛋白間結(jié)合有望是理解細(xì)胞間通道性質(zhì)的關(guān)鍵,。對(duì)多細(xì)胞結(jié)構(gòu)的結(jié)構(gòu)完整性和生物化學(xué)完整性至關(guān)重要的是，縫隙連接將指導(dǎo)人們?cè)谖磥?lái)開(kāi)發(fā)出分子療法來(lái)治療相關(guān)疾病指明方向,。(生物谷：Bioon.com)
本文編譯自Gauging the forces between cells
doi: 10.1016/j.jmb.2012.07.004
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High-Speed Atomic Force Microscopy: Cooperative Adhesion and Dynamic Equilibrium of Junctional Microdomain Membrane Proteins
Adai Colom1, Ignacio Casuso1, Thomas Boudier2, Simon Scheuring
Junctional microdomains, paradigm for membrane protein segregation in functional assemblies, in eye lens fiber cell membranes are constituted of lens-specific aquaporin-0 tetramers (AQP04) and connexin (Cx) hexamers, termed connexons. Both proteins have double function to assure nutrition and mediate adhesion of lens cells. Here we use high-speed atomic force microscopy to examine microdomain protein dynamics at the single-molecule level. We found that the adhesion function of head-to-head associated AQP04 and Cx is cooperative. This finding provides first experimental evidence for the mechanistic importance for junctional microdomain formation. From the observation of lateral association–dissociation events of AQP04, we determine that the enthalpic energy gain of a single AQP04–AQP04 interaction in the membrane plane is − 2.7 kBT, sufficient to drive formation of microdomains. Connexon association is stronger as dynamics are rarely observed, explaining their rim localization in junctional microdomains.
