利用電場調變整合素蛋白極化及引導細胞移動現象

Abstract

電刺激被臨床使用在疼痛的治療以及促進傷口癒合。在骨科的處理上，施予電場可以促進骨頭的癒合以及促進韌帶的復原。在實驗中，我們選用物理治療上時常使用的電刺激波形並檢視對於前十字韌帶纖維母細胞移動以及型態的影響，我們選用的大部分刺激參數都可以增加纖維母細胞的移動，然而對於移動方向上有著十分顯著的差異。此外，前十字韌帶纖維母細胞只有在直流電刺激下會造成細胞有延伸排列的情形。實驗的結果使我們發現細胞移動速度與方向性上有不耦合的情形，這可能是因為不同的機制在進行調控。我們發現整合素蛋白在電場誘發細胞方向性改變的傳導機轉上扮演重要的控制角色，另外也發現整合素蛋白的重新排列也會帶動RhoA排列在負極的現象，這表示電場藉由整合素蛋白的不平均分佈調控了下游重要的傳導分子的分布狀態。本篇研究有助於了解物理治療臨床電療在細胞層面的行為影響，以及建立與釐清電場誘導細胞方向性改變的傳導機轉與整合素蛋白的關係。

Electrical stimulation is clinically used for the treatment of pain and to promote wound healing. In orthopaedic practices, applied electric fields (EFs) promote bone healing and improve lapine ligament repair in vivo. In the current study, several stimulation waveforms used in physical therapy were adapted to examine their effects on anterior cruciate ligament fibroblast (ACLF) migration and morphology. Most of the waveforms we tested resulted in enhanced fibroblast migration, while their effects on migration directionality were noticeably different. Furthermore, ACLFs elongation and alignment were only found in the DC groups. These findings suggest a decoupling of migration speed and directionality, which may arise from disparate mechanisms. We found that integrin acts as a major player of EF-induced directionality. We also found that integrin redistribution mediate the cathodal redistribution of RhoA. This introduces EF mediates one of the major signaling molecules, which is downstream from the integrin asymmetrically, with stronger redistribution on the cathode, is highly significant functionally. Results from this study may benefit our understanding the electro-therapy treatment on cell behavior and the relation between integrin and EF-induced directionality.