力學(xué)生物學(xué)劉波生物醫(yī)學(xué)工程系生命現(xiàn)象化學(xué)現(xiàn)象物理現(xiàn)象生物化學(xué)分子生物學(xué)物質(zhì)運(yùn)動(dòng)力學(xué)規(guī)律？

生物力學(xué)是應(yīng)用于生物學(xué)的力學(xué)。生物力學(xué)探索的是了解生命系統(tǒng)的力學(xué)。絕大多數(shù)生物力學(xué)工作的目的是為了豐富生命系統(tǒng)的基本知識(shí)并對(duì)其進(jìn)行某種人為干涉。

——馮元楨世界生物力學(xué)之父工程生物生理變化基因作用力學(xué)分析生物綜合MatchinggeneactivitywithbiomechanicsandphysiologyPNAS,2002,99(5):2603Two-waystreet

力學(xué)生物學(xué)（mechanobiology）是研究力學(xué)環(huán)境（刺激）對(duì)生物體健康、疾病或損傷的影響，研究生物體的力學(xué)信號(hào)感受和響應(yīng)機(jī)制，闡明機(jī)體的力學(xué)過(guò)程與生物學(xué)過(guò)程如生長(zhǎng)、重建、適應(yīng)性變化和修復(fù)等之間的相互關(guān)系，從而發(fā)展有療效的或有診斷意義的新技術(shù)。stresscell壓力切應(yīng)力牽張力脈動(dòng)頻率？力學(xué)生物學(xué)

mechanobiology高血壓、動(dòng)脈粥樣硬化、腦卒中、心肌梗塞、心肌肥厚、血栓形成、心功能衰竭等心血管病

高血壓病>1億,70年代8～12%→現(xiàn)在17～22%

高血壓并發(fā)腦卒中600萬(wàn)，新發(fā)病人>150萬(wàn)/年,

死亡>100萬(wàn)/年

我國(guó)心血管病的防治費(fèi)用>1000億高血壓動(dòng)脈粥樣硬化、腦卒中、心肌梗塞、心肌肥厚、血栓形成、心腎功能衰竭等血管重建remodeling

細(xì)胞遷移、肥大、增殖、凋亡、細(xì)胞表型、形態(tài)結(jié)構(gòu)與功能的變化力學(xué)生物學(xué)研究手段

Researchmethods應(yīng)力加載(stressapplication)Animalmodel：自發(fā)性高血壓大鼠SHR腎缺血高血壓模型腹主動(dòng)脈縮窄低血壓模型頸動(dòng)脈縮窄低剪切應(yīng)力模型鼠尾懸吊低重力模型力學(xué)生物學(xué)研究手段應(yīng)力加載stressapplicationCellmodel：StretchShearstress（flowchamber）Pressure血管應(yīng)力培養(yǎng)模型Organculturemodel優(yōu)點(diǎn)closetorealcondition

andtheforcecanbecontrolledaccurately缺點(diǎn)thesystemisverycomplexMorphologyandimaginganalyze常規(guī)生化檢測(cè)（RealtimePCR、westernblotting、ELISA、proteomics…）Mechanicaldetection(hardness,elasticity,compliance)ControlForce檢測(cè)手段(TestFacility)研究目的

(ResearchPurpose)探討力學(xué)條件下細(xì)胞基本功能變化Stress-inducedalternationofbasiccellularfunction探討應(yīng)力相關(guān)疾病發(fā)病機(jī)理（高血壓、失重….）Themechanismofpathogenesis尋找應(yīng)力相關(guān)信號(hào)蛋白潛在藥物靶點(diǎn)

Potentialdrugtargets組織工程（人工血管、骨再生….）Tissueengineering力學(xué)生物學(xué)在血管組織工程研究中的運(yùn)用：Applicationofmechanobiologyinvasculartissueengineering應(yīng)力介導(dǎo)干細(xì)胞定向分化Stress-induceddifferentiationofstemcells生物材料的應(yīng)力篩選Stressscreeningofbiologicalmaterials三維培養(yǎng)組織工程血管的力學(xué)改造Mechanicalreconstructionof3Dculturedtissueengineeredbloodvessels力學(xué)生物學(xué)新進(jìn)展熒光蛋白技術(shù)在力學(xué)生物學(xué)中的應(yīng)用OsamuShimomuraMartinChalfieRogerY.Tsien美國(guó)WoodsHole海洋生物學(xué)實(shí)驗(yàn)室哥倫比亞大學(xué)加州大學(xué)圣地亞哥分校從水母(Aequoreavictoria)體內(nèi)發(fā)現(xiàn)的發(fā)光蛋白。分子質(zhì)量為26kDa，由238個(gè)氨基酸構(gòu)成，第65～67位氨基酸(Ser-Tyr-Gly)形成發(fā)光團(tuán)，是主要發(fā)光的位置。當(dāng)它受到藍(lán)光照射時(shí)，會(huì)吸收藍(lán)光的部分能量，然后發(fā)射出綠色的熒光其發(fā)光團(tuán)的形成不具物種專一性，發(fā)出熒光穩(wěn)定，且不需依賴任何輔因子或其他基質(zhì)而發(fā)光。綠色熒光蛋白greenfluorescenceprotein(GFP)在綠色熒光蛋白基礎(chǔ)上發(fā)展起來(lái)多種顏色熒光蛋白：綠色熒光線形蟲(chóng)綠色熒光蜜蜂

綠色熒光小鼠

綠色熒光恒河猴

綠色熒光帝王蝎綠色熒光兔黃色熒光水母黃色熒光煙草綠色熒光豬克隆紅色熒光貓紅色熒光狗熒光熱帶魚熒光蛋白在生物學(xué)研究中的應(yīng)用熒光蛋白連接靶蛋白分子：遠(yuǎn)紅外熒光蛋白監(jiān)測(cè)腫瘤生長(zhǎng)優(yōu)缺點(diǎn)：可以活細(xì)胞動(dòng)態(tài)觀察可以顯示靶蛋白在亞細(xì)胞水平的定位一定程度上可以顯示靶蛋白表達(dá)量多少其熒光強(qiáng)弱與每個(gè)細(xì)胞的新陳代謝狀態(tài)有關(guān)不能檢測(cè)靶蛋白的活性原理：CFP的發(fā)射光譜與YFP的吸收光譜有相當(dāng)?shù)闹丿B，當(dāng)它們足夠接近時(shí)，用CFP的吸收波長(zhǎng)激發(fā)，CFP的發(fā)色基團(tuán)將會(huì)把能量高效率地共振轉(zhuǎn)移至YFP的發(fā)色基團(tuán)上，所以CFP的發(fā)射熒光將減弱或消失，主要發(fā)射將是YFP的熒光。兩個(gè)發(fā)色基團(tuán)之間的能量轉(zhuǎn)換效率與它們之間的空間距離的6次方成反比，對(duì)空間位置的改變非常靈敏。fluorescenceresonanceenergytransfer熒光共振能量轉(zhuǎn)移技術(shù)FRET作為共振能量轉(zhuǎn)移供、受體對(duì)，熒光物質(zhì)必須滿足以下條件：受、供體的激發(fā)光波長(zhǎng)要足夠分得開(kāi)；供體的發(fā)光光譜與受體的激發(fā)光譜要重疊。Annu.Rev.Biomed.Eng.2008.10:1–38FRET

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