上皮細胞在基底上因受彈性、邊緣和界面三個效應的共同作用，可以形成形態(tài)豐富的粘著單層。細胞通過粘著斑感受其外界環(huán)境，可看作是細胞與基質(zhì)之間的機械連接。之前的力生物學研究主要集中于單個細胞，而來自美國賓州大學的張宿林教授等卻探索了多細胞的受力反應，探討了單層細胞作為整體如何傳遞和分配牽引力。他們基于分子的熱力學模型、單層-底物彈性的整合和力-介導的粘著形成，建立了熱力學模型，提出了粘著形成機制，并通過顯微觀察牽引力作用等實驗測量方法來驗證該模型的預測結(jié)果。他們發(fā)現(xiàn)，細胞和基底之間的耦合（通過粘附分子）屬于高度非線性耦合；細胞外牽引力和細胞間張力與細胞單層尺寸相關(guān)，也與基質(zhì)剛度有關(guān)，提示細胞內(nèi)、外分子之間存在相互信息交流；在細胞單層邊緣，粘著斑通過與細胞外基質(zhì)的相互作用產(chǎn)生了強大牽引力，而在細胞單層的中央，細胞應激水平上升的同時僅遭受到較低牽引力。這些結(jié)果將有助于解釋局部環(huán)境如何影響細胞決策，也將促進上皮組織中諸如形態(tài)發(fā)生或集體遷移等更為復雜問題的研究。綜上，該模型為多用途計算框架奠定了堅實的基礎(chǔ)，可用來揭示多細胞上皮形態(tài)發(fā)生和疾病的分子起源。

Active cell-matrix coupling regulates cellular force landscapes of cohesive epithelial monolayers

Tiankai Zhao,Yao Zhang,Qiong Wei,Xuechen Shi,Peng Zhao,Long-Qing Chen&Sulin Zhang

Abstract Epithelial cells can assemble into cohesive monolayers with rich morphologies on substrates due to competition between elastic, edge, and interfacial effects. Here we present a molecularly based thermodynamic model, integrating monolayer and substrate elasticity, and force-mediated focal adhesion formation, to elucidate the active biochemical regulation over the cellular force landscapes in cohesive epithelial monolayers, corroborated by microscopy and immunofluorescence studies. The predicted extracellular traction and intercellular tension are both monolayer size and substrate stiffness dependent, suggestive of cross-talks between intercellular and extracellular activities. Our model sets a firm ground toward a versatile computational framework to uncover the molecular origins of morphogenesis and disease in multicellular epithelia.