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

0854288E。这个由生物传感和生物工程/CBET计划颁发的NSF奖项支持哈佛大学的Eric Mazur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性中的作用。他们使用双光子聚合来制备3D基质，在三维空间中研究细胞的黏附和迁移。细胞迁移研究正在发生耐人寻味的新转折，新出现的研究显示，细胞在二维和三维迁移方式上存在显著差异。这样的研究对于了解各种生理和病理过程，如癌症的进展、转移和组织再生非常重要。这项提议的主要目标是开发一种合成的三维细胞外基质(ECM)，允许对生化和生物物理线索进行独立和精确的空间控制。具体地说，他们将开发双光子聚合系统来制备具有不同物理化学性质的三维基质。然后，他们将通过以受控方式改变细胞外基质的几个参数来对细胞迁移进行系统研究。将研究孔的大小和形状、机械硬度、ECM壁的粘附肽浓度、基质的降解对细胞运动和粘附力的影响。这种方法将使他们能够在微米和亚微米尺度上精确、独立地控制结构以及各种黏附和机械参数，以系统地研究它们在细胞迁移中的作用。最后，拟议的工作将证明这种方法的广泛适用性，以孤立地研究各种细胞和组织过程，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.