以複合式微結構平台來探討細胞在彈性梯度上的移動行為

Abstract

細胞與其機械環境的交互作用在許多生理機制中扮演重要角色，包括形態發育，免疫反應, 傷口癒合以及腫瘤細胞惡性轉移等。近期研究顯示，細胞有優先朝機械性質較硬的區域去遷移的現象，稱為durotaxis。本研究的目的為發展一個有連續彈性梯度的系統，是以膠原蛋白膠體為基礎的複合微結構基材，來促使細胞產生durotaxis，並更進一步探討其機制。研究結果顯示細胞durotaxis的表現與其彈性梯度的強度相關。此外也發現durotaxis 只會出現在細胞密度較低時；細胞與細胞的交互作用會造成durotaxis表現下降。藥物抑制的研究顯示細胞受基材機械性質影響而產生方向性遷移的行為是與Rho及myosin所調控細胞收縮的機制相關。本系統為全新的實驗平台來幫助深入探討基材彈性梯度對細胞反應與其內部分子機制的影響。

Cell interaction with their physical environment has been shown to play an important role in physiological processes, including morphogenesis, immune response, wound healing, and tumor metastasis. Recent studies have demonstrated that preferential migration of cells toward mechanically stiff regions; a process known as durotaxis. However, much of this phenomenon is still not fully understood. In this study, we developed a novel system of a continuous stiffness gradient with a collagen hydrogel-based composite microstructural substrate. Our results indicated that induction of durotaxis depends on the magnitude of the elasticity jump. In addition, our results provide a quantitative confirmation that increases in cell density reduce cell durotaxis, which can be observed only at low cell density, where there is less cell-cell interaction. Pharmacologic inhibition studies suggested that cell migration directed by substrate mechanical stiffness was regulated by a Rho- and myosin-dependent cell contractility mechanism. This novel platform allows for better understanding of the cellular response to substrate stiffness gradients and the underlying molecular mechanisms.