Using two-photon polymerization for the fabrication of 3D matrices for cell migration studies

0854288 e。这项由生物传感和生物工程/CBET项目颁发的国家科学基金会奖支持哈佛大学Eric Mazur教授和David Mooney教授的工作，他们使用双光子制造技术研究材料结构和物理特性在3D细胞-细胞相互作用和运动中的作用。他们利用双光子聚合法制备三维矩阵，在三维空间中研究细胞的粘附和迁移。细胞迁移研究正在出现有趣的新转折，新兴的研究揭示了细胞在二维和三维迁移方式上的显著差异。这些研究对于了解各种生理和病理过程，如癌症的进展、转移和组织再生是重要的。本提案的主要目标是开发一种合成的三维细胞外基质（ECM），允许独立和精确的生化和生物物理信号的空间控制。具体来说，他们将开发双光子聚合系统来制造具有不同物理和化学性质的三维矩阵。然后，他们将以可控的方式改变ECM的几个参数，对细胞迁移进行系统的研究。将研究孔隙大小和形状、机械刚度、ECM壁粘附肽浓度、基质降解对细胞运动和粘附的影响。这种方法将允许他们在微米和亚微米尺度上对结构以及各种粘附和机械参数进行精确，独立的控制，以系统的方式研究它们在细胞迁移中的作用。最后，提出的工作将证明这种方法的广泛适用性，以研究不同的细胞和组织过程在隔离，以解决生物学中的新问题。

0854288E. MazurThis NSF award by the Biosensing and Bioengineering/CBET program supports work by Professors Eric Mazur and David Mooney at Harvard University to study the role of material architecture and physical properties in 3D cell-cell interactions and motility using a two- photon fabrication technique. Using two-photon polymerization to fabricate 3D matrices, they study cell adhesion and migration in three dimensions. Cell migration research is taking intriguing new turns and emerging studies are revealing marked differences in the way that cells migrate in two versus three dimensions. Such studies are important to understand a variety of physiological and pathological processes such as progression of cancer, metastasis, and tissue regeneration. The main goal of this proposal is to develop a synthetic three-dimensional extracellular matrix (ECM) that permits independent and precise spatial control of biochemical and biophysical cues. Specifically, they will develop two-photon polymerization system to fabricate three-dimensional matrix with varying physical and chemical properties. They will then perform a systematic study on cell migration by varying several parameters of the ECM in a controlled way. The effects of pore size and shape, mechanical-stiffness, adhesion peptide concentration of the ECM walls, degradation of the matrix on cell motility, and adhesion will be studied. This approach will allow them to have a precise, independent control over architecture as well as various adhesion and mechanical parameters at a micrometer and submicrometer scale to study their role in cell migration in a systematic manner. Finally, the proposed work will demonstrate the broad applicability of this approach to study various cell and tissue processes in isolation in order to address novel problems in biology.