Patterning ECM microstructure to investigate 3D cellular dynamics under multiplexed mechanochemical guidance.
Patterning ECM microstructure to investigate 3D cellular dynamics under multiplexed mechanochemical guidance.
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DOI：
10.12688/f1000research.125171.1
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发表时间：
2022
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背景：生化和生物物理因素共同调节许多生理过程中的细胞动力学。因此，在采用基于细胞的体外测定来模拟生理过程时，必须包括多重微环境线索。 方法：为了满足这一需求，我们开发了一个 3D 细胞培养模块化平台，即细胞迁移和培养测定微环境模块化控制 (MC33A)，该平台分别以趋化性和接触引导的形式结合了定向化学和机械线索。利用 MC33A 的功能，我们研究了乳腺癌细胞在 3D 工程细胞外基质 (ECM) 中遵循血清趋化梯度的迁移和形态。 结果：我们发现，当通过与血清梯度相同方向的接触引导促进趋化性时，细胞表现出运动维数降低和高度拉长的椭圆体形状。当ECM排列方向偏离血清梯度方向时，趋化运动显着受到抑制，细胞的形态通常更加突出和圆形。 结论：这些例子证明 MC33A 作为设计复杂的细胞微环境的强大工具，将推动药物开发、再生医学和生物工程其他研究领域基于细胞的分析的最先进水平。
Background: Biochemical and biophysical factors jointly regulate the cellular dynamics in many physiological processes. It is therefore imperative to include multiplexed microenvironment cues when employing {in vitro} cell-based assays to model physiological processes. Methods: To meet this need, we have developed a modular platform of 3D cell culture, Modular Control of Microenvironment for Cell Migration and Culture Assay (MC33A), that incorporates directed chemical and mechanical cues in the forms of chemotaxis and contact guidance, respectively. Taking advantage of the functionalities of MC33A, we study the migration and morphology of breast cancer cells in 3D engineered extracellular matrix (ECM) following a serum gradient for chemotaxis. Results: We show that when chemotaxis is facilitated by contact guidance in the same direction as the serum gradient, cells demonstrate dimensional-reduction in their motility and highly elongated ellipsoidal shape. When the direction of ECM alignment diverges from the direction of serum gradient, chemotactic motion is significantly suppressed, and cells are generally more protrusive and rounded in their morphology. Conclusions: These examples demonstrate MC33A as a powerful tool for engineering complex microenvironments of cells that will advance the state-of-the-art of cell-based analysis in drug development, regenerative medicine, and other research areas in bioengineering.